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Enzyme Nomenclature
Information on EC 3.1.26.13 - retroviral ribonuclease H
for references in articles please use BRENDA:EC3.1.26.13
Word Map on EC 3.1.26.13
- 3.1.26.13
- dttp
- hiv-rt
-
template-primer
- 3'-azido-3'-deoxythymidine
-
primer-template
-
polypurine
- 2'-deoxynucleoside
-
aztmp
-
nonnucleoside
- medicine
- analysis
- drug development
- pharmacology
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
3.1.26.13
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RECOMMENDED NAME
GeneOntology No.
retroviral ribonuclease H
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
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-
-
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Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
cleavage reaction mechanism and substrate specificity of HIV-1 RNase H, overview
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CAS REGISTRY NUMBER
COMMENTARY
9050-76-4
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
652865, 652907, 665720, 666034, 695644, 695645, 696181, 696183, 696189, 696192, 696194, 698692, 698694, 698701, 699509, 699893, 699894, 700927, 701025, 701113, 701116, 701216, 701386, 708108, 709451, 710132, 710144, 710674, 728978, 729231, 729354, 729677, 729791, 730043, 730167, 730217, 730486, 730494, 730514
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derived from clade B; derived from clade C; derived from CRF01 A_E
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HIV-1
650155, 690924, 713770, 713774, 714475, 714972, 715532, 715864, 716067, 716827, 716993, 716994, 716995
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
-
antiviral activity of 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione is probably due to the RNase H inhibition
malfunction
-
severe defects in RNase H activity alone, exemplified by the P236L mutant, appear sufficient to cause a substantial reduction in fitness. Reductions in reverse transcriptase content decrease both polymerization and RNase H activity in virions
malfunction
-
PEGylation as a tool for engineering the M-MuLV RT derivative deficient in RNase H activity, overview
malfunction
-
patients treated with nucleoside reverse transcriptase inhibitors develop classical patterns of resistance-associated mutations in the pol domain. Thymidine analogue mutations, TAMs, arise with zidovudine and stavudine treatment, which encompass M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N. Different patterns of thymidine analogue mutations accumulate in patients, which segregate into two distinct pathways named TAM-1 and TAM-2. The TAM-1 pathway includes M41L, L210W and T215Y, whereas the TAM-2 pathway includes D67N, K70R, T215F and K219Q/E/N
malfunction
-
RNase H-deficient HIV-1 reverse transcriptase shows altered error specificity during DNA-dependent DNA synthesis
malfunction
-
patients treated with nucleoside reverse transcriptase inhibitors develop classical patterns of resistance-associated mutations in the pol domain. Thymidine analogue mutations, TAMs, arise with zidovudine and stavudine treatment, which encompass M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N. Different patterns of thymidine analogue mutations accumulate in patients, which segregate into two distinct pathways named TAM-1 and TAM-2. The TAM-1 pathway includes M41L, L210W and T215Y, whereas the TAM-2 pathway includes D67N, K70R, T215F and K219Q/E/N
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physiological function
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increasing the stoichiometry of RNase H relative to the amount of functional DNA polymerase by virions engineered to contain phenotypic mixtures of wild-type and RNase H catalytic site point mutant D524N reverse transcriptase, has minimal effects on direct repeat deletion frequency. DNA synthesis is error prone when directed principally by RNase H mutant reverse transcriptase, suggesting a role for RNase H catalytic integrity in the fidelity of intracellular reverse transcription
physiological function
-
the retroviral RNase H degrades the RNA template following first strand synthesis, generates primers for second strand synthesis, and eliminates the t-RNA primer
physiological function
-
the reverse transcriptase generates an RNA/DNA hybrid that is a substrate for RNase H. The RNA/DNA hybrid is degraded to generate a nascent minus-strand single-stranded DNA. As DNA synthesis proceeds, RNase H degrades the RNA strand
physiological function
-
the process of reverse transcription involves the copying of the single-stranded RNA of the viral genome into double-stranded DNA. This requires that reverse transcriptase is able to act at times as a RNA-dependent DNA polymerase, a DNA-dependent DNA polymerase, and as an RNase H that cleaves the RNA of RNA/DNA hybrids. These activities are coordinated temporally and spatially. As all three of these processes are absolutely required for the successful completion of reverse transcription, role of RNase H in (+)-strand priming and in strand transfer and (-)-strand primer removal, overview
physiological function
-
the process of reverse transcription involves the copying of the single-stranded RNA of the viral genome into double-stranded DNA. This requires that reverse transcriptase is able to act at times as a RNA-dependent DNA polymerase, a DNA-dependent DNA polymerase, and as an RNase H that cleaves the RNA of RNA/DNA hybrids. These activities are coordinated temporally and spatially. As all three of these processes are absolutely required for the successful completion of reverse transcription, role of RNase H in (+)-strand priming and in strand transfer and (-)-strand primer removal, overview
physiological function
the enzyme activity and substrate specificity is controlled by the RNase H primer grip, and the width of the minor groove and the trajectroy of the RNA:DNA, both in a sequence-dependent manner
physiological function
-
RNase H activity is essential for virus infectivity
additional information
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catalytically important residues of the RNase H activity are Asp524 and Asp583
additional information
-
HIV-1 reverse transcriptase has two associated activities, DNA polymerase and RNase H, both essential for viral replication and validated drug targets
additional information
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the active site of RNase H consists of four highly conserved carboxylate residues, D443, E478, D498, and D549, and requires Mg2+ or Mn2+ for its catalytic activity
additional information
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RT is a unique viral protein containing two enzymatic properties, i.e. RNase H cleavage activity and RNA- and DNA-dependent DNA polymerase activity
additional information
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the RNase H activity, which degrades RNA from RNA/DNA hybrids endonucleolytically, is part of the HIV reverse transcriptase
additional information
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role of RNase H activity in drug resistance, the RNase H domains can affect the susceptibility of RT to non-nucleoside reverse transcriptase inhibitors and nucleos(t)ide reverse transcriptase inhibitors. Furthermore, RNase H activity itself is implicated in the mechanism of resistance to nucleoside reverse transcriptase inhibitors such as 3'-azidodeoxythymidine, and also to non-nucleoside reverse transcriptase inhibitors such as nevirapine. RNase H exists as a domain in the larger enzyme HIV-1 reverse transcriptase, structure and function of HIV-1 RNase H, overview
additional information
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Q294 is highly conserved in HIV-2 isolates
additional information
the polypurine tract, PPT, a purine-rich segment from the HIV-1 genome, is resistant to RNase H cleavage and is used as a primer for second DNA strand synthesis. PPT-enzyme complex structure, detailed overview
additional information
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RT is a unique viral protein containing two enzymatic properties, i.e. RNase H cleavage activity and RNA- and DNA-dependent DNA polymerase activity
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-end-labeled 267 nt-long RNA annealed to 20 nt-long synthetic DNA + H2O
?
-
-
-
-
?
5'-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC-dGdGdGdGdAdTdCdCdTdCdTdAdG-3'/3'-dTdCdGdAdGdCdCdAdTdGdGdG-dCdCdCdCdTdAdGdGdAdGdTdC-5' + H2O
5'-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC/dGdGdGdGdAdTdCdCdTdCdTdAdG-3' + 3'-dTdCdGdAdGdCdCdAdTdGdGdG/dCdCdCdCdTdAdGdGdAdGdTdC-5'
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model substrate, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication, contains sequences from the HIV genome and sequences unrelated to the HIV viral genome
hydrolysis of the phosphodiester bond at the DNA-RNA junction
-
?
5'-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA-dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3'/3'-dGdAdCdAdAdGdCdCdCdGdCdGdGdT-dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5' + H2O
5'-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA/dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3' + 3'-dGdAdCdAdAdGdCdCdCdGdCdGdGdT/dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5'
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model substrate containing sequences from the HIV genome, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication. The DNA-extended RNA was a template and was annealed to a DNA oligonucleotide that primed reverse transcription of the RNA in the template
hydrolysis of the phosphodiester bond at the DNA-RNA junction
-
?
5-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC-dGdGdGdGdAdTdCdCdTdCdTdAdG-3 + 3-dTdCdGdAdGdCdCdAdTdGdGdG-dCdCdCdCdTdAdGdGdAdGdTdC-5' + H2O
?
5-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA-dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3 + 3-dGdAdCdAdAdGdCdCdCdGdCdGdGdT-dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5 + H2O
?
poly(A)+ mRNA primed with oligo(dT) + H2O
double-stranded DNA copies between 1.3 and 9.9 kilobases in length + ?
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multifunctional enzyme containing RNase H and reverse transcriptase activity
-
-
?
poly(dT)-poly(rA) + H2O
?
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substrate poly(dC)-poly(rG) is markedly preferred over substrate poly(dT)-poly(rA)
-
-
?
RNA-DNA hybrid containing the polypurine tract + H2O
?
-
extension of the polypurine tract primer by at least 2 nucleotides is sufficient for recognition and correct cleavage by RNase H at the RNA-DNA junction to remove the primer. Primer removal occurs by cleavage one nucleotide away from the RNA-DNA junction. The same polypurine tract specificity determinants responsible for generation of the polypurine tract primer also direct polypurine tract primer removal. Once the primer has been extended and removed from the nascent plus-strand DNA, reinitiation at the resulting plus-strand primer terminus does not occur
-
-
?
5-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC-dGdGdGdGdAdTdCdCdTdCdTdAdG-3 + 3-dTdCdGdAdGdCdCdAdTdGdGdG-dCdCdCdCdTdAdGdGdAdGdTdC-5' + H2O
?
-
model substrate, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication, contains sequences from the HIV genome and sequences unrelated to the HIV viral genome
hydrolysis of the substrate to leave a single ribonucleotide 5-phosphate at the 5-terminus of the model DNA genome
-
?
5-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC-dGdGdGdGdAdTdCdCdTdCdTdAdG-3 + 3-dTdCdGdAdGdCdCdAdTdGdGdG-dCdCdCdCdTdAdGdGdAdGdTdC-5' + H2O
?
-
model substrate, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication, contains sequences from the HIV genome and sequences unrelated to the HIV viral genome
hydrolysis of the substrate to leave a single ribonucleotide 5-phosphate at the 5-terminus of the model DNA genome
-
?
5-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA-dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3 + 3-dGdAdCdAdAdGdCdCdCdGdCdGdGdT-dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5 + H2O
?
-
model substrate containing sequences from the HIV genome, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication. The DNA-extended RNA was a template and was annealed to a DNA oligonucleotide that primed reverse transcription of the RNA in the template
hydrolysis of the substrate to leave a single ribonucleotide 5'-phosphate at the 5'-terminus of the model DNA genome
-
?
5-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA-dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3 + 3-dGdAdCdAdAdGdCdCdCdGdCdGdGdT-dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5 + H2O
?
-
model substrate containing sequences from the HIV genome, designed to be structurally similar to the DNA-extended tRNA created by initiation of minus-strand DNA synthesis during retroviral replication. The DNA-extended RNA is a template and is annealed to a DNA oligonucleotide that primed reverse transcription of the RNA in the template
hydrolysis of the substrate to leave a single ribonucleotide 5-phosphate at the 5-terminus of the model DNA genome
-
?
RNA-DNA hybrid + H2O
?
-
5'-GTTTTCTTTTCCCCCCTGAC-3'-fluorescein/5'-CAAAAGAAAAGGGGGGACUG-3'-dabcyl
-
-
?
additional information
?
-
-
evaluation of activity by enzyme's ability to select and extend the 3' polypurine tract primers into (+) strand DNA. Evaluation via concerted and two-step reactions for (+) strand priming, the latter of which allows discrimination between selection end extension events
3' polypurine tract primer selection appears to represent a specialized form of RNase H activity that is more sensitive to minor structural alterations within this domain
-
-
additional information
?
-
-
no substrate: single-stranded RNA or the DNA component of DNA-RNA hybrids. Products consist primarily of monomers, dimers, and trimers with 3'-OH groups
-
-
-
additional information
?
-
-
the HIV polymerase and RNase H active sites are separated by a distance equivalent to the length of a 15-nucleotide RNA-DNA heteroduplex
-
-
-
additional information
?
-
-
a nick separating an upstream RNA and a downstream RNA annealed to DNA is essentially ignored by RNase H, indicating that the RNA 5' end at a nick is not sufficient to position 5' end-directed cleavages. Cleavage sites that are located close to the 5' end of the downstream RNA are not recognized in the absence of the upstream RNA, and the 5' ends of the shorter upstream RNAs enhance cleavage at these sites. The recognition of an internal cleavage site depends on local sequence features found both upstream and downstream of the cleavage site, designated as the -1/+1 position. Preferred nucleotides have been identified in the flanking sequences spanning positions -14 to +1
-
-
-
additional information
?
-
-
interdependence of the polymerase and RNase H activities of HIV-1 reverse transcription during viral DNA synthesis
-
-
-
additional information
?
-
-
RNase H acts at or about 14 to 18 nucleotides from the 5' end of the template, the cleavage site for the RNase H is therefore held at around this distance behind the DNA polymerase activity. For the intact protein, the RNase H and reverse transcriptase activities may work in a coupled or coordinate manner. More than 80% of the residual 5' oligonucleotides remain base paired to the RNA-directed DNA product. Under certain conditions, these short RNAs can act as efficient primers for an associated DNA-directed DNA synthesis in the reverse direction
-
-
-
additional information
?
-
-
study on specificity of RNase H cleavage by use of synthetic DNA-RNA hybrids based on the same 81-base RNA template. First series of RNase H substrates is prepared with complementary DNA oligonucleotides of different lengths, ranging from 6 to 20 nucleotides, all of which share a common 5' end and are successively shorter at their 3' ends. The second series of oligonucleotides has a common 3' end but shorter 5' ends. The DNA oligonucleotides in the third series are all 20 bases long but have non-complementary stretches at either the 5' end, 3' end, or both ends. Enzyme cleaves fairly efficiently if the duplex region is at least eight bases long, but not if it is shorter. Although enzyme requires the substrate to have a region of RNA-DNA duplex, Moloney murine leukemia virus RT can cleave RNA outside the region that is part of the RNA-DNA duplex. The polymerase domain of HIV-1 RT uses certain mismatched segments of RNA-DNA to position the enzyme for RNase H cleavage. A mismatched region near the RNase H domain can interfere with RNase H cleavage, cleavage is usually but not always more efficient if the mismatched segment is deleted
-
-
-
additional information
?
-
-
substrate heteropolymeric 90-nt 5' end-labeled RNA template-annealed to a 36-nt DNA primer is cleaved by wild-type p66/p51 RT precisely at the RNA/DNA junction to liberate a 20-nt (+) strand DNA
-
-
-
additional information
?
-
-
substrates consist of SP6 runoff transcripts from a portion of the gag region of the HIV-1 genome hybridized to complementary single-stranded DNA from either an M 13 subclone or a phagemid transcription vector subclone. The corresponding hybrids are fully base-paired
products formed from the fully complementary hybrid consist of a nonuniform distribution of oligonucleotides ranging in size from 4 to 15 nt
-
-
additional information
?
-
-
substrates consist of SP6 runoff transcripts from a portion of the gag region of the HIV-1 genome hybridized to complementary single-stranded DNA from either an M 13 subclone or a phagemid transcription vector subclone. The corresponding hybrids carry a 5'-mismatch of seven nucleotides
products are a few prominent intermediates of 24-42 nt in size with relatively little accumulation of larger products
-
-
additional information
?
-
-
the recognition and precise cleavage of the polypurine tract of the human immunodeficiency virus type 1 is an essential step in HIV-1 reverse transcription. Mutations at positions 2 and 5 of the 3'-end of the polypurine tract do significantly alter the cleavage specificity at the polypurine tract/U3 junction. The structure of the polypurine tract primer, rather than the base-specific contacts between the polypurine tract and HIV-1 RT, are the primary determinants of RNase H cleavage specificity at the polypurine tract/U3 junction
-
-
-
additional information
?
-
-
the selection of 5' end-directed cleavage sites by retroviral RNases H results from a combination of nucleotide sequence, permissible distance, and accessibility to the RNA 5' end. Enzyme strongly prefers A or U at the +1 position and C or G at the -2 position, and A is disfavored at the -4 position. 5' End-directed cleavages occur when sites are positioned between the 13th and 20th nucleotides from the RNA 5' end. The extent of 5' end-directed cleavages observed in substrates containing a free recessed RNA 5' end is most comparable to substrates with a gap of 2 or 3 bases between the upstream and downstream RNAs
-
-
-
additional information
?
-
-
5'end-directed RNase H of reverse transcriptase
-
-
-
additional information
?
-
-
HIV-1 reverse transcriptase has two enzymatic functions, DNA polymerase and RNase H activities
-
-
-
additional information
?
-
-
RNase H functions as an endonuclease that specifically cleaves the RNA moiety of RNA/DNA hybrids, substrate binding and reaction mechanism, overview
-
-
-
additional information
?
-
-
cleavage of DNA-RNA and RNA-DNA primer templates
-
-
-
additional information
?
-
-
RNA-DNA duplex substrate from a 41-mer 5'-labeled 32P-heteropolymeric RNA template kim40R annealed to complementary 32-mer DNA oligomer kim32D
-
-
-
additional information
?
-
-
RNA-DNA substrate in a tRNA removal assay, the cleavage patterns for the recombinant HIV-1 reverse transcriptase and mutant p51-G-TCR construct correspond to the release of the 11mer RNA, corresponding with the authentic cleavage identified in vivo. The relative activity of the isolated HIV-1 RNaseH(p51-G-TCR) is comparable to that of the full-length HIV reverse transcriptase
-
-
-
additional information
?
-
RNA/DNA hybrid duplex substrate
-
-
-
additional information
?
-
-
substrate is 18-nucleotide 3'-fluourescein-labeled RNA annealed to a complementary 18-nucleotide 5'-dabsyl-labeled DNA
-
-
-
additional information
?
-
-
the tC5U-p12 hybrid is used as reaction substrate the RNase H activity
-
-
-
additional information
?
-
-
conserved residues in the connection subdomain and C-terminal ribonuclease H, RNase H, domain of HIV-1 RT contact the nascent DNA primer and modulate the trajectory of the template relative to the RNase H catalytic center. Within the RNase H domain, these residues include Thr473, Glu475, Lys476, Tyr501, and Ile505, while His539 and Asn474 interact with the scissile phosphate of the RNA template,m substrate recognition and binding, overview
-
-
-
additional information
?
-
-
a 5'-32P-labeled AZT-MP chain-terminated RNA/DNA template/primer substrate
-
-
-
additional information
?
-
-
cleavage of DNA-RNA and RNA-DNA primer templates
-
-
-
additional information
?
-
-
RNA-DNA duplex substrate from a 41-mer 5'-labeled 32P-heteropolymeric RNA template kim40R annealed to complementary 32-mer DNA oligomer kim32D
-
-
-
additional information
?
-
RNA/DNA hybrid duplex substrate
-
-
-
additional information
?
-
-
RNase H functions as an endonuclease that specifically cleaves the RNA moiety of RNA/DNA hybrids, substrate binding and reaction mechanism, overview
-
-
-
additional information
?
-
-
a nick separating an upstream RNA and a downstream RNA annealed to DNA is essentially ignored by RNase H, indicating that the RNA 5' end at a nick is not sufficient to position 5' end-directed cleavages. Cleavage sites that are located close to the 5' end of the downstream RNA are not recognized in the absence of the upstream RNA, and the 5' ends of the shorter upstream RNAs enhance cleavage at these sites. The recognition of an internal cleavage site depends on local sequence features found both upstream and downstream of the cleavage site, designated as the -1/+1 position. Preferred nucleotides have been identified in the flanking sequences spanning positions -11 to +1
-
-
-
additional information
?
-
-
study on specificity of RNase H cleavage by use of synthetic DNA-RNA hybrids based on the same 81-base RNA template. First series of RNase H substrates is prepared with complementary DNA oligonucleotides of different lengths, ranging from 6 to 20 nucleotides, all of which share a common 5' end and are successively shorter at their 3' ends. The second series of oligonucleotides has a common 3' end but shorter 5' ends. The DNA oligonucleotides in the third series are all 20 bases long but have non-complementary stretches at either the 5' end, 3' end, or both ends. Enzyme cleaves fairly efficiently if the duplex region is at least eight bases long, but not if it is shorter. Although enzyme requires the substrate to have a region of RNA-DNA duplex, Moloney murine leukemia virus RT can cleave RNA outside the region that is part of the RNA-DNA duplex. The polymerase domain of Moloney murine leukemia virus RT does not use the same mismatched segments to define the position for RNase H cleavage
-
-
-
additional information
?
-
-
the selection of 5' end-directed cleavage sites by retroviral RNases H results from a combination of nucleotide sequence, permissible distance, and accessibility to the RNA 5' end. Enzyme strongly prefers A or U at the +1 position and C or G at the -2 position. 5' End-directed cleavages occurr when sites are positioned between the 13th and 20th nucleotides from the RNA 5' end. The extent of 5' end-directed cleavages observed in substrates containing a free recessed RNA 5' end is most comparable to substrates with a gap of 2 or 3 bases between the upstream and downstream RNAs
-
-
-
additional information
?
-
-
Moloney murine leukemia virus reverse transcriptase, M-MuLV RT, is a domain structured enzyme that has the N-terminally located DNA polymerization activity and C-terminally located RNase H activity, which interferes with the efficient synthesis of long cDNA molecules
-
-
-
additional information
?
-
-
Moloney murine leukemia virus reverse transcriptase, MMLV RT, shows DNA polymerization activity and RNase H activity. Stabilization of the reverse transcriptase activity by eliminating the RNase H activity, overview
-
-
-
additional information
?
-
-
retroviral reverse transcriptase also possesses a ribonuclease H activity, an enzyme which cleaves the RNA strand of RNA/DNA hetroduplex
-
-
-
additional information
?
-
-
DNA binding by M-MuLV RT assay using 5'-end labeled 48/36 bp RNA-DNA oligonucleotide duplex, method, overview. RNA-DNA hybrid binding and 5'-end labeled 48/36 bp RNA-DNA oligonucleotide duplex by M-MuLV RT derivatives, overview
-
-
-
additional information
?
-
-
substrate is a 3H-UTP-labeled RNA: RNA-DNA hybrid, synthesis, overview
-
-
-
additional information
?
-
-
the active site of the RNase H function contains four acidic residues, D443, E478, D498, and D549, that likely coordinate two divalent metal ions that are essential for catalysis
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
5'end-directed RNase H of reverse transcriptase
-
-
-
additional information
?
-
-
HIV-1 reverse transcriptase has two enzymatic functions, DNA polymerase and RNase H activities
-
-
-
additional information
?
-
-
RNase H functions as an endonuclease that specifically cleaves the RNA moiety of RNA/DNA hybrids, substrate binding and reaction mechanism, overview
-
-
-
additional information
?
-
-
conserved residues in the connection subdomain and C-terminal ribonuclease H, RNase H, domain of HIV-1 RT contact the nascent DNA primer and modulate the trajectory of the template relative to the RNase H catalytic center. Within the RNase H domain, these residues include Thr473, Glu475, Lys476, Tyr501, and Ile505, while His539 and Asn474 interact with the scissile phosphate of the RNA template,m substrate recognition and binding, overview
-
-
-
additional information
?
-
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RNase H functions as an endonuclease that specifically cleaves the RNA moiety of RNA/DNA hybrids, substrate binding and reaction mechanism, overview
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-
additional information
?
-
-
Moloney murine leukemia virus reverse transcriptase, M-MuLV RT, is a domain structured enzyme that has the N-terminally located DNA polymerization activity and C-terminally located RNase H activity, which interferes with the efficient synthesis of long cDNA molecules
-
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additional information
?
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Moloney murine leukemia virus reverse transcriptase, MMLV RT, shows DNA polymerization activity and RNase H activity. Stabilization of the reverse transcriptase activity by eliminating the RNase H activity, overview
-
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additional information
?
-
-
retroviral reverse transcriptase also possesses a ribonuclease H activity, an enzyme which cleaves the RNA strand of RNA/DNA hetroduplex
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
additional information
Mg2+
-
required, with more than 90% of maximum activity between 4 and 12 mM
Mg2+
-
two Mg2+ ions as essential in formation of the active catalytic complex
Mg2+
-
Mn2+ is preferred over Mg2+. One-metal catalytic mechanism for the Mn2+/Mg2+-dependent activities
Mn2+
-
solid state strucuture, two Mn2+ ions bound to the RNase H active site
Mn2+
-
modeling of the HIV-1 RNase H domain in complex with an inhibitor and two Mn2+ cations from crystal structure of manicol-bound enzyme
Mn2+
-
activation at 0.01-1 mM, inhibitory above. Mn2+ is preferred over Mg2+. One-metal catalytic mechanism for the Mn2+/Mg2+-dependent activities
additional information
-
in the crystal structure, two divalent metal cations bind in the active site surrounded by a cluster of four conserved acidic amino acid residues
additional information
metal coordination, structure, overview
additional information
-
the active site of the RNase H function contains four acidic residues, D443, E478, D498, and D549, that likely coordinate two divalent metal ions that are essential for catalysis
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-5,7-dihydroxy-2-(2-hydroxy-1-(phenylsulfonyl)propan-2-yl)-9-methyl-3,4-dihydro-1H-benzo[7]annulen-6(2H)-one
-
-
(2Z)-4-[1-(4-fluorobenzyl)-4-oxo-7-(pyrrolidin-1-yl)-1,4-dihydroquinolin-3-yl]-2-hydroxy-4-oxobut-2-enoic acid
-
-
(4-N,N-dimethylaminobenzoyl)-2-hydroxy-1-naphthyl hydrazone
-
specific
(5E)-6-[1-(2,4-dimethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
-
-
(5E)-6-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
-
-
(5E)-6-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
-
-
(5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
-
-
(5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoic acid
-
-
(5E)-6-[1-(4-fluorobenzyl)-4-phenyl-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoic acid
-
-
(6,6,12,12,18,18,18-heptaoxido-5,7,11,13,17-pentaoxa-6l5,12l5,18l5-triphosphaoctadec-1-yl)phosphonate
-
-
1,2-bis[(3-oxobutan-2-yl)oxy]anthracene-9,10-dione
-
20% inhibition
1,2-dihydroxyanthracene-9,10-dione
-
i.e. alizarine, 8% inhibition
1-(3-[[(4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]methyl]-4-methoxyphenyl)ethanone
-
-
1-hydroxy-4-((4-(morpholinomethyl)phenyl)amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-((4-(pyridin-4-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-([[3-(4-morpholinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-([[3-(4-morpholinylmethyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-([[4-(4-morpholinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-([[4-(4-pyridinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-[[4-(4-morpholinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-2(1H)-one
-
-
1-hydroxy-4-[[4-(quinolin-3-yl)phenyl]amino]pyrido[2,3-d]pyrimidin-2(1H)-one
-
GSK5724, exceptional RNase H inhibitory potency
10,12,15,16-tetrahydroxy-8-methoxy-11-methyl-2-phenyl-6,7-dihydrotetraceno[1,2-g]phthalazine-1,9,14(2H)-trione
-
-
2',3'-dideoxy-3'-triaz-2-en-2-ium-3-id-1-yl-3,4-dihydrothymidine
-
-
2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-guanosine
-
40% inhibition of RNase H at 0.05 microM
2'-deoxy-P-thioguanylyl-(3'->5')-guanosine
-
65% inhibition of RNase H at 0.05 microM
-
2,3,7-trihydroxy-6-(3-nitrobenzyl)cyclohepta-2,4,6-trien-1-one
-
-
2,7-dihydroxy-4-isopropyl-cyclohepta-2,4,6-triene
-
i.e. beta-thujaplicinol
2-(1,2-dihydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(2,3-dihydro-1H-inden-1-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-(2,3-dihydro-1H-inden-2-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-(2-benzylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(2-ethanesulfonyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(2-ethylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-(3-bromo-4-methoxybenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
-
inhibition of enzymatic activity, but no antiviral effect
2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide
-
-
2-hydroxy-(4H)-isoquinoline-1,3-dione
-
inhibits RNase H in vitro with submicromolar potency
2-hydroxy-4-(2-phenyl)ethylisoquinoline-1,3(2H,4H)-dione
-
enol-form
2-hydroxy-4-(3-phenyl)propylisoquinoline-1,3(2H,4H)-dione
-
mixture of th mixed ketoenol forms or keto-form
2-hydroxy-4-(4-methylbenzyl)isoquinoline-1,3(2H,4H)-dione
-
mixture of th mixed ketoenol forms or keto-form
2-hydroxy-4-(4-trifluoromethylbenzyl)isoquinoline-1,3(2H-4H)-dione
-
keto-form
2-hydroxy-4-butylisoquinoline-1,3(2H,4H)-dione
-
mixture of th mixed ketoenol forms or keto-form
2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H, 4H)-dione
-
inhibits RNase H in vitro with nanomolar potency
2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione
-
shows antiviral activity
2-oxo-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl 5-nitrofuran-2-carboxylate
-
-
2-oxo-2-(tetrahydrofuran-2-ylamino)ethyl 5-nitrofuran-2-carboxylate
-
-
2-oxo-2-[(2,3,4-trichlorophenyl)amino]ethyl benzyl(phenyl)carbamodithioate
-
-
2-oxo-2-[(2,3,4-trichlorophenyl)amino]ethyl dibenzylcarbamodithioate
-
-
2-oxo-2-[(2-phenylpropan-2-yl)amino]ethyl 5-nitrofuran-2-carboxylate
-
-
2-[(2,3,4-trichlorophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
-
inhibitor indentified by FRET-based high-throughput screening assay
2-[(2,4-dichlorophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
-
-
2-[(2,4-dimethylphenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
-
; inhibitor indentified by FRET-based high-throughput screening assay
2-[(2-bromo-5-chloro-1-benzothiophen-3-yl)methyl]-5,6-dihydroxypyrimidine-4-carboxylic acid
-
-
2-[(2-methoxy-5-methylphenyl)amino]-2-oxoethyl benzyl(phenyl)carbamodithioate
-
-
2-[(2-methyl-1-phenylpropan-2-yl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[(2-methylbutan-2-yl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[(3-cyanophenyl)amino]-2-oxoethyl benzyl(phenyl)carbamodithioate
-
-
2-[(3-cyanophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
-
-
2-[(4-hydroxybenzyl)(tetrahydrofuran-2-ylmethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[2-(2-fluoro-benzylamino)-1-hydroxy-1-methyl-ethyl]-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
2-[2-(4-bromophenyl)-2-oxoethoxy]-9,10-dioxo-9,10-dihydroanthracen-1-yl acetate
-
-
2-[2-(biphenyl-4-yl)-2-oxoethoxy]-9,10-dioxo-9,10-dihydroanthracen-1-yl acetate
-
-
2-[4-benzyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]pyridine
-
; inhibitor indentified by FRET-based high-throughput screening assay
2-[4-benzyl-5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl]pyridine
-
-
2-[benzyl(tetrahydrofuran-2-ylmethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[bis(4-methoxyphenyl)(phenyl)methoxy]ethyl 2-cyanoethyl dipropan-2-ylphosphoramidoite
-
-
2-[tert-butyl(2-phenylethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(3-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(3-oxo-3-phenylpropyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(3-phenylpropyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(4-fluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(4-methoxybenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(4-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(pentafluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl(phenyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl[2-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl[3-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[tert-butyl[4-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[[2-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[[4-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-[[4-(benzyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
3'-[(E)-[2-(3,4,5-trihydroxybenzoyl)hydrazinylidene]methyl]biphenyl-4-carboxylic acid
-
-
3,4-dihydroxy-N'-[(E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide
-
-
3,9,11,14,15-pentahydroxy-7-methoxy-10-methyl-5,6-dihydrobenzo[9,10]tetrapheno[2,3-c]furan-1,8,13(3H)-trione
-
-
3-(furan-2-yl)-4-(4-methoxybenzyl)-5-[[4-(trifluoromethyl)benzyl]sulfanyl]-4H-1,2,4-triazole
-
-
3-(furan-2-yl)-4-phenyl-5-[[4-(trifluoromethyl)benzyl]sulfanyl]-4H-1,2,4-triazole
-
-
3-cyclopentyl-1,4-dihydroxy-1,8-naphthyridin-2(1H)-one
-
3-[2-(4-bromophenyl)-2-oxoethoxy]-1,8-dihydroxy-6-methylanthracene-9,10-dione
-
-
3-[4-(2-methyl-imidazo[4,5-c]pyridin-1-yl)-benzyl]-3H-benzothiazol-2-one
-
-
4-((cyclopropylmethyl)amino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
4-(([1,1'-biphenyl]-4-ylmethyl)amino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
4-(4,4-difluoropiperidin-1-yl)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
4-([1,1'-biphenyl]-4-ylamino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
4-([[4-benzyl-5-(furan-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
-
-
4-benzyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
-
keto-form; mixture of th mixed ketoenol forms
4-benzyl-3-(benzylsulfanyl)-5-(furan-2-yl)-4H-1,2,4-triazole
-
; inhibitor indentified by FRET-based high-throughput screening assay
4-benzyl-3-(benzylsulfanyl)-5-(thiophen-2-yl)-4H-1,2,4-triazole
-
; inhibitor indentified by FRET-based high-throughput screening assay
4-benzyl-3-(benzylsulfanyl)-5-phenyl-4H-1,2,4-triazole
-
; inhibitor indentified by FRET-based high-throughput screening assay
4-benzyl-3-(furan-2-yl)-5-[(4-methoxybenzyl)sulfanyl]-4H-1,2,4-triazole
-
-
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-(furan-2-yl)-4H-1,2,4-triazole
-
-
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
-
; inhibitor indentified by FRET-based high-throughput screening assay
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-phenyl-4H-1,2,4-triazole
-
-
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
-
-
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-phenyl-4H-1,2,4-triazole
-
inhibitor indentified by FRET-based high-throughput screening assay
4-hexyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
-
keto-form; mixture of th mixed ketoenol forms
4-tert-butyl-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]benzohydrazide
-
-
4-[1-4-[(4-fluorophenyl)methyl]-7-[N-(3-chloroprop-1-yl)-piperazin-1-yl]-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
35% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(dimethylamino)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
72% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(dimethylamino)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
26% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(morpholin-4-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
0.7% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-acetylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
22% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-acetylpiperazin-1-yl)-4-(1h)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
30% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-ethylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
34% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-ethylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
63% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-methylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
44% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(N-methylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
41% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(piperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
44% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(piperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
-
18% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-(thiomorpholin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
74% inhibition at 0.01 mM
4-[1-[(4-fluorophenyl)methyl]-7-[N-(3-chloroprop-1-yl)piperazin-1-yl]-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
-
78% inhibition at 0.01 mM
4-[[(4-fluorophenyl)methyl]amino]-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
4-[[4'-(aminomethyl)biphenyl-4-yl]methyl]-1-hydroxy-1,8-naphthyridin-2(1H)-one
-
-
4-[[4-([4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl]amino)pyrimidin-2-yl]amino]benzonitrile
-
i.e. TMC278 or rilpivirine, enzyme-bound structure, overview
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylaminoethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylsulfanylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
5,7-dihydroxy-2-(1-hydroxy-ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
-
5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
i.e. manicol, the alpha-hydroxytroplone potently and specifically inhibits HIV RT ribonuclease H, enzyme-bound structure, overview
5-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide
-
-
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
6-[1-(4-fluorophenyl)methyl-1H-pyrrol-2-yl]-2,4-dioxo-5-hexenoic acid ethyl ester
-
i.e. RDS-1643, shows relatively weak but selective inhibitory activity against RNase H
6-[4-(diethylamino)phenoxy]-3-[ethoxy(hydroxy)methyl]-1,4-dihydroxy-1,8-naphthyridin-2(1H)-one
-
9,10-dioxo-2-(2-oxo-2-phenylethoxy)-9,10-dihydroanthracen-1-yl acetate
-
-
9,10-dioxo-2-(2-oxopropoxy)-9,10-dihydroanthracen-1-yl acetate
-
10% inhibition
9,10-dioxo-2-(prop-2-en-1-yloxy)-9,10-dihydroanthracen-1-yl acetate
-
-
9,10-dioxo-2-(prop-2-yn-1-yloxy)-9,10-dihydroanthracen-1-yl acetate
-
-
9,10-dioxo-2-[(2-oxopentan-3-yl)oxy]-9,10-dihydroanthracen-1-yl acetate
-
inhibits the RNase H function and is inactive on the DNA polymerase function
9,10-dioxo-2-[(3-oxobutan-2-yl)oxy]-9,10-dihydroanthracen-1-yl acetate
-
-
9,10-dioxo-9,10-dihydroanthracene-1,2-diyl diacetate
-
12% inhibition
actinomycin D
-
limits the enzyme to the first strand synthesis
delaviridine
-
a nonnucleoside reverse transcriptase inhibitor
Dextran sulfate
-
more potent inhibitor of RNase H than of reverse transcriptase. 50% infective dose corresponds to 0.1 nM
-
ethyl (2Z)-4-[1-(4-fluorobenzyl)-4-oxo-7-(pyrrolidin-1-yl)-1,4-dihydroquinolin-3-yl]-2-hydroxy-4-oxobut-2-enoate
-
-
ethyl (5E)-6-[1-(2,4-dimethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
-
-
ethyl (5E)-6-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
-
selectively inhibits RNase H activity in the low micromolar range
ethyl (5E)-6-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
-
-
ethyl (5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
-
-
ethyl (5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoate
-
-
ethyl (5E)-6-[1-(4-fluorobenzyl)-4-phenyl-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoate
-
-
F3284-8495
-
specific inhibitor with low micromolar potency in vitro
guanylyl-(3'->5')-guanosine
-
89% inhibition of RNase H at 0.05 microM
heparin
-
more potent inhibitor of RNase H than of reverse transcriptase. 50% infective dose corresponds to 0.5-1.5 nM
methyl 2-hydroxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
-
-
N-(4-chlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide
-
-
NSC727447
-
mutation T473C increases sensitivity of the enzyme for NSC727447 by 50fold
P-thioguanylyl-(3'->5')-guanosine
-
50% inhibition of RNase H at 0.05 microM
-
sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-[2-(4-nitrophenyl)ethyl]guanosine
-
69% inhibition of RNase H at 0.05 microM
-
tenofovir disoproxil fumarate
-
a nucleoside reverse transcriptase inhibitor
-
xylan polysulfate
-
more potent inhibitor of RNase H than of reverse transcriptase. 50% infective dose corresponds to 8 nM
-
2,7-dihydroxy-4-(propan-2-yl)cyclohepta-2,4,6-trien-1-one
-
inhibition of enzymatic activity, but no antiviral effect
2-(3,4-dichlorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
-
inhibition of enzymatic activity, but no antiviral effect
2-(3,4-dichlorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
-
-
2-hydroxyisoquinoline-1,3(2H,4H)-dione
-
inhibition of enzymatic activity, but no antiviral effect
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
-
; inhibitor indentified by FRET-based high-throughput screening assay
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
-
-
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
-
inhibitor has little effect on bacterial RNase H activity in vitro
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
-
-
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
-
additionally inhibits HIV-1 replication effectively. Inhibitor has little effect on bacterial RNase H activity in vitro
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
-
-
beta-thujaplicinol
-
slow-binding RNase H inhibitor with noncompetitive kinetics that forms a tropylium ion that interacts favorably with reverse transcriptase and the RNA:DNA substrate
beta-thujaplicinol
-
shows submicromolar inhibitory activity against RNase H
efavirenz
-
second generation non-nucleoside reverse transcriptase inhibitor, shows the effect of simultaneously reorienting domain motions and obstructing the p66 thumb fluctuations
efavirenz
-
stronger effect of mutation N348I on RNase H susceptibility to nevirapine as compared with efavirenz
ethyl 1,4-dihydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate
interactions between MK1 and two Mn2+ ions, which are coordinated by the RNase H active site residues D443, E478, D498, and D549, binding structure, overview. In addition, G444, S499, A538, H539, V552, and S553 contribute to the binding site
ethyl 1,4-dihydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate
-
-
nevirapine
-
non-nucleoside RT inhibitors such as nevirapine interfere directly with the global hinge-bending mechanism that controls the cooperative motions of the p66 fingers and thumb subdomains. The net effect of nevirapine binding is to change the direction of domain movements rather than suppress their mobilities
nevirapine
-
a non-nucleoside RT inhibitor, NNRTI, stronger effect of mutation N348I on RNase H susceptibility to nevirapine as compared with efavirenz
nevirapine
a nonnucleoside reverse transcriptase inhibitor, NNRTI
sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-naphthalen-1-ylguanosine
-
61% inhibition of RNase H at 0.05 microM
-
sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-naphthalen-1-ylguanosine
-
11% inhibition of RNase H at 0.05 microM
-
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
-
additionally inhibits DNA strand transfer and DNA polymerase activity of the retroviral reverse transcriptase
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
-
inhibits RNase H activity, does not significantly affect DNA polymerase activity of reverse transcriptase. In the absence of DNA synthesis, [2-(4-chlorophenyl)hydrazinylidene]propanedioic acid interferes with the translocation, or repositioning, of the enzyme on the RNA-DNA template duplex. Inhibitor is highly specific for human immunodeficiency virus. The dicarboxylic acid moiety is essential for activity, and Mg2+ chelates directly with a Kd value of 2.4 mM
additional information
-
synthesis of 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives as inhibitors of the RNase H activity of the reverse transcriptase of HIV-1, docking, study, overview. No inhibition by keto-5i and 5l
-
additional information
-
identification and evaluation of thiocarbamate and triazole inhibitors targeting RNase H activity of HIV reverse transcriptase, overview
-
additional information
-
design, synthesis, and screening of derivatives of 5-nitro-furan-2-carboxylic acid as inhibitors of the RNAse H activity of HIV-1 reverse transcriptase, overview. Modulation of the 5-nitro-furan-2-carboxylic moiety results in a drastic decrease in inhibitory potency. Binding mode of active derivatives, in which three oxygen atoms aligned in a straight form at the nitro-furan moiety are coordinated to two divalent metal ions located at RNase H reaction site. The nitro-furan-carboxylic moiety is one of the critical scaffolds for RNase H inhibition. Cytotoxicity of the synthesized compounds, overview
-
additional information
-
non-nucleoside RT inhibitors, NNRTIs, bind to an allosteric site that is 10 A from the polymerase active site and 60 A from the RNase H active site
-
additional information
-
no inhibition by 5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, 5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, 2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, and 2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
-
additional information
structures of naphthyridinone-containing inhibitors bound to the RNase H active site, overview. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain
-
additional information
-
C-terminal domain mutations reduce RNase H activity either directly by affecting the RNase H cleavage activity of the enzyme, or indirectly by affecting the overall positioning of the template/primer strand, which in turn affects RNase H activity, template switching, polymerization and/or nucleotide excision. Effects of enzyme mutations on treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, detailed overview. Nucleoside reverse transcriptase inhibitors are nucleoside analogues that lack the 3' OH on the sugar ring and competitively block reverse transcription by causing chain termination during DNA polymerization. Nucleoside reverse transcriptase inhibitors are prodrugs that require intracellular phosphorylation to the 5'-triphosphate formed by host cell kinases in order to become active. Nonnucleoside reverse transcriptase inhibitors in general are non-competitive inhibitors of RT that bind to a hydrophobic pocket near the polymerase active site, inducing conformational changes that inhibit RT enzymatic activity. Inhibition mechanisms of the two inhibitor classes, overview
-
additional information
-
mechanisms of catalysis and drug inhibition of polymerase and RNase H functions of RT by nucleos(t)ide reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs, and molecular mechanisms of drug resistance, detailed overview
-
additional information
-
discovery and development of bona fide RNase H inhibitors, overview
-
additional information
-
inhibitory potency and binding of dumbbell oligonucleotides to MoMuL virus RNase H, overview. The best dumbbell oligonucleotide, inhibitor contained phosphorothioate residues in both the loops
-
additional information
-
magnesium chelating 2-hydroxyisoquinoline-1,3(2H,4H)-diones, as inhibitors of HIV-1 integrase and/or the HIV-1 reverse transcriptase ribonuclease H domain, overview. 2-Hydroxyisoquinoline-1,3(2H,4H)-dione forms a 1:1 complex with Mg2+, but a 1:2 complex with Mn2+,
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
efavirenz
-
stimulates reverse transcriptase RNase H activity. Efavirenz stimulates DNA 3'-directed and RNA 5'-directed RNase H activity
nucleocapsid protein NCp7
-
enhances ribonuclease H activity and changes the specificity of hydrolysis. As a model, the NCp7 binds to the DNA strand and through interaction with HIV-1 RT facilitates the delivery of the DNA-RNA duplex into the RNase H site for cleavage, thereby altering the rate and location of RNase H cleavage
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000029
RNA-DNA hybrid
-
mutant enzyme Y501A, at pH 7.8 and 37°C
-
0.00003
RNA-DNA hybrid
-
mutant enzyme N474A, at pH 7.8 and 37°C
-
0.000041
RNA-DNA hybrid
-
mutant enzyme R557A, at pH 7.8 and 37°C
-
0.000085
RNA-DNA hybrid
-
mutant enzyme R448A, at pH 7.8 and 37°C
-
0.0001
RNA-DNA hybrid
-
mutant enzyme Q475A, at pH 7.8 and 37°C
-
0.000126
RNA-DNA hybrid
-
wild type enzyme, at pH 7.8 and 37°C
-
additional information
additional information
-
presteady-state kinetic analyses, overview
-
additional information
additional information
-
pre-steady-state kinetics, overview
-
additional information
poly(rA)/oligo(dT)
-
apparent binding constant 3500 per mM
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.024
poly(rA)n-poly(dT)n
-
37°C, mutant p66/p51C280P; 37°C, mutant p66/p51C280W
-
0.029
poly(rA)n-poly(dT)n
-
37°C, mutant p66C280P/p51C280P; 37°C, mutant p66C280W/p51
-
0.004
RNA-DNA hybrid
-
mutant enzyme Y501A, at pH 7.8 and 37°C
-
0.04
RNA-DNA hybrid
-
mutant enzyme N474A, at pH 7.8 and 37°C
-
0.18
RNA-DNA hybrid
-
mutant enzyme Q475A, at pH 7.8 and 37°C
-
0.42
RNA-DNA hybrid
-
mutant enzyme R557A, at pH 7.8 and 37°C
-
0.73
RNA-DNA hybrid
-
mutant enzyme R448A, at pH 7.8 and 37°C
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00014
beta-thujaplicinol
-
presence of Mg2+ and DNA:RNA hybrid, pH 8.0
0.0115
sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-[2-(4-nitrophenyl)ethyl]guanosine
-
-
-
additional information
additional information
-
non competitive inhibition kinetics of alizarine derivatives, overview
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00051
(2S)-5,7-dihydroxy-2-(2-hydroxy-1-(phenylsulfonyl)propan-2-yl)-9-methyl-3,4-dihydro-1H-benzo[7]annulen-6(2H)-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.0193
(5E)-6-[1-(2,4-dimethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0192
(5E)-6-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.087
(5E)-6-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0161
(5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.028
(5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0077
(5E)-6-[1-(4-fluorobenzyl)-4-phenyl-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoic acid
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0008
1-(3-[[(4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]methyl]-4-methoxyphenyl)ethanone
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0002
1-hydroxy-4-((4-(morpholinomethyl)phenyl)amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000079
1-hydroxy-4-((4-(pyridin-4-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.0002
1-hydroxy-4-([[3-(4-morpholinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000398
1-hydroxy-4-([[3-(4-morpholinylmethyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.0001
1-hydroxy-4-([[4-(4-morpholinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000016
1-hydroxy-4-([[4-(4-pyridinyl)phenyl]methyl]amino)pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.00005
1-hydroxy-4-[[4-(4-morpholinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000003
1-hydroxy-4-[[4-(quinolin-3-yl)phenyl]amino]pyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0006
2,7-dihydroxy-4-(propan-2-yl)cyclohepta-2,4,6-trien-1-one
Human immunodeficiency virus 1
-
-
0.0019
2-(1,2-dihydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00096
2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.0061
2-(2,3-dihydro-1H-inden-1-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0055
2-(2,3-dihydro-1H-inden-2-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0013
2-(2-benzylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.0005
2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00024
2-(2-ethanesulfonyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00038
2-(2-ethylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.0012
2-(3,4-dichlorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
Human immunodeficiency virus 1
-
-
0.0009
2-(3-bromo-4-methoxybenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
Human immunodeficiency virus 1
-
-
0.018
2-(tert-butylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0071
2-amino-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.002
2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0668
2-hydroxy-4-(3-phenyl)propylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.08
2-hydroxy-4-(4-methylbenzyl)isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0427
2-hydroxy-4-(4-trifluoromethylbenzyl)isoquinoline-1,3(2H-4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0132
2-hydroxy-4-butylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0388
2-hydroxy-4-ethylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0185
2-hydroxy-4-isopropylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.000061
2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H, 4H)-dione
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.000061
2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione
Moloney murine leukemia virus
-
pH 8.0, 37°C
0.0336
2-hydroxy-4-pentylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0468
2-hydroxy-4-propylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0301
2-hydroxyisoquinoline-1,3(2H,4H)-dione magnesium complex
Moloney murine leukemia virus
-
pH 8.0, 37°C
-
0.0043
2-oxo-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0019
2-oxo-2-(phenylamino)ethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0132
2-oxo-2-(propan-2-yloxy)ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0042
2-oxo-2-(tetrahydrofuran-2-ylamino)ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0266
2-oxo-2-[(2,3,4-trichlorophenyl)amino]ethyl benzyl(phenyl)carbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0033
2-oxo-2-[(2,3,4-trichlorophenyl)amino]ethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0082
2-oxo-2-[(2-phenylpropan-2-yl)amino]ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0033
2-[(2,3,4-trichlorophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH 8.0, 25°C
0.0058
2-[(2,4-dichlorophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0019
2-[(2,4-dimethylphenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.00017
2-[(2-bromo-5-chloro-1-benzothiophen-3-yl)methyl]-5,6-dihydroxypyrimidine-4-carboxylic acid
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0083
2-[(2-methoxy-5-methylphenyl)amino]-2-oxoethyl benzyl(phenyl)carbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0043
2-[(2-methyl-1-phenylpropan-2-yl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0058
2-[(2-methylbutan-2-yl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0114
2-[(3-cyanophenyl)amino]-2-oxoethyl benzyl(phenyl)carbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0047
2-[(3-cyanophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.005
2-[(4-hydroxybenzyl)(tetrahydrofuran-2-ylmethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0012
2-[2-(2-fluoro-benzylamino)-1-hydroxy-1-methyl-ethyl]-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.021
2-[2-(4-bromophenyl)-2-oxoethoxy]-9,10-dioxo-9,10-dihydroanthracen-1-yl acetate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.1
2-[2-(biphenyl-4-yl)-2-oxoethoxy]-9,10-dioxo-9,10-dihydroanthracen-1-yl acetate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0017
2-[4-benzyl-5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]pyridine
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.0026
2-[4-benzyl-5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl]pyridine
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0077
2-[benzyl(tetrahydrofuran-2-ylmethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0142
2-[tert-butyl(2-phenylethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0098
2-[tert-butyl(3-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.05
2-[tert-butyl(3-oxo-3-phenylpropyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.05
2-[tert-butyl(3-phenylpropyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0085
2-[tert-butyl(4-fluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0075
2-[tert-butyl(4-methoxybenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0069
2-[tert-butyl(4-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0068
2-[tert-butyl(pentafluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0009
2-[tert-butyl(phenyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.009
2-[tert-butyl[2-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0085
2-[tert-butyl[3-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.008
2-[tert-butyl[4-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0128
2-[[2-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0087
2-[[4-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.05
2-[[4-(benzyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0001
3'-[(E)-[2-(3,4,5-trihydroxybenzoyl)hydrazinylidene]methyl]biphenyl-4-carboxylic acid
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0219
3,3-dimethyl-2-oxobutyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37°C
0.0065
3-(furan-2-yl)-4-(4-methoxybenzyl)-5-[[4-(trifluoromethyl)benzyl]sulfanyl]-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0047
3-(furan-2-yl)-4-phenyl-5-[[4-(trifluoromethyl)benzyl]sulfanyl]-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.029
3-[2-(4-bromophenyl)-2-oxoethoxy]-1,8-dihydroxy-6-methylanthracene-9,10-dione
Human immunodeficiency virus 1
-
-
0.000398
4-((cyclopropylmethyl)amino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.00001
4-(([1,1'-biphenyl]-4-ylmethyl)amino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000501
4-(4,4-difluoropiperidin-1-yl)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000032
4-([1,1'-biphenyl]-4-ylamino)-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.004
4-([[4-benzyl-5-(furan-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0002 - 0.2
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
0.0149
4-benzyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0012
4-benzyl-3-(benzylsulfanyl)-5-(furan-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.00021
4-benzyl-3-(benzylsulfanyl)-5-(thiophen-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.001
4-benzyl-3-(benzylsulfanyl)-5-phenyl-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.0038
4-benzyl-3-(furan-2-yl)-5-[(4-methoxybenzyl)sulfanyl]-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0028
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-(furan-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.001
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25°C; pH not specified in the publication, temperature not specified in the publication
0.006
4-benzyl-3-[(4-chlorobenzyl)sulfanyl]-5-phenyl-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.001
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-phenyl-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25°C
0.045
4-heptyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0035
4-tert-butyl-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]benzohydrazide
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0066
4-[1-[(4-fluorophenyl)methyl]-7-(dimethylamino)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0068
4-[1-[(4-fluorophenyl)methyl]-7-(morpholin-4-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0033
4-[1-[(4-fluorophenyl)methyl]-7-(N-acetylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0262
4-[1-[(4-fluorophenyl)methyl]-7-(N-ethylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0185
4-[1-[(4-fluorophenyl)methyl]-7-(N-methylpiperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid ethyl ester
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0287
4-[1-[(4-fluorophenyl)methyl]-7-(piperazin-1-yl)-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0057
4-[1-[(4-fluorophenyl)methyl]-7-[N-(3-chloroprop-1-yl)piperazin-1-yl]-4-(1H)-quinolinon-3-yl]-2-hydroxy-4-oxo-2-butenoic acid
Human immunodeficiency virus 1
-
in 50 mM Tris-HCl, pH 8.0, at 37°C
0.0032
4-[5-(benzoylamino)thiophen-2-yl]-2,4-dioxobutanoic acid
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.000158
4-[[(4-fluorophenyl)methyl]amino]-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22°C
0.000045
4-[[4'-(aminomethyl)biphenyl-4-yl]methyl]-1-hydroxy-1,8-naphthyridin-2(1H)-one
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.0012
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylaminoethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00093
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylsulfanylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00082
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00911
5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.00068
5,7-dihydroxy-2-(1-hydroxy-ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one
Human immunodeficiency virus 1
-
pH 8.0, 37°C
0.0026 - 0.0322
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
0.00013
6-[1-(4-fluorophenyl)methyl-1H-pyrrol-2-yl]-2,4-dioxo-5-hexenoic acid ethyl ester
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.039
9,10-dioxo-2-(2-oxo-2-phenylethoxy)-9,10-dihydroanthracen-1-yl acetate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.013
9,10-dioxo-9,10-dihydroanthracene-1,2-diyl dibenzoate
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0082
ethyl (5E)-6-[1-(2,4-dimethylbenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0073
ethyl (5E)-6-[1-(2-chlorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0063
ethyl (5E)-6-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0086
ethyl (5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.0112
ethyl (5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.008
ethyl (5E)-6-[1-(4-fluorobenzyl)-4-phenyl-1H-pyrrol-3-yl]-2,4-dioxohex-5-enoate
Human immunodeficiency virus 1
-
at pH 7.8 and 37°C
0.00011
ethyl 1,4-dihydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.04
sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-naphthalen-1-ylguanosine, sodium 2'-deoxy-2'-fluoro-P-thioadenylyl-(3'->5')-N-[2-(4-nitrophenyl)ethyl]guanosine
Human immunodeficiency virus 1
-
-
-
0.0388
2-hydroxy-4-methylisoquinoline-1,3(2H,4H)-dione
Moloney murine leukemia virus
-
pH 8.0, 37°C
0.07
2-hydroxy-4-methylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0002
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
Human immunodeficiency virus 1
-
pH 8.0, 25°C
0.0002
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
Human immunodeficiency virus 1
-
pH and temperature not specified in the publication
0.2
4-([[4-benzyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl]methyl)pyridine
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.001
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0059
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH not specified in the publication, temperature not specified in the publication
0.0078
4-hexyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.038
4-hexyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37°C
0.0038
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
Human immunodeficiency virus 1
-
-
0.0084
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
Moloney murine leukemia virus
-
-
0.0265
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
Human immunodeficiency virus 1
-
-
0.0296
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
Human immunodeficiency virus 1
-
-
0.0026
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
Human immunodeficiency virus 1
-
-
0.0086
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
Moloney murine leukemia virus
-
-
0.0267
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
Human immunodeficiency virus 1
-
-
0.0322
5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
Human immunodeficiency virus 1
-
-
0.000186
ARK-2452
Human immunodeficiency virus 1
-
pH 8.0, 37°C, purified recombinant mutant p51-G-TCR construct
-
0.00047
ARK-2452
Human immunodeficiency virus 1
-
pH 8.0, 37°C, purified recombinant wild-type HIV-1 reverse transcriptase RNase H
-
0.00007
beta-thujaplicinol
Human immunodeficiency virus 1
-
mutant enzyme Y501A, at pH 7.8 and 37°C
0.00009
beta-thujaplicinol
Human immunodeficiency virus 1
-
mutant enzyme N474A, at pH 7.8 and 37°C
0.00015
beta-thujaplicinol
Human immunodeficiency virus 1
-
mutant enzyme R448A, at pH 7.8 and 37°C
0.000176
beta-thujaplicinol
Human immunodeficiency virus 1
-
pH 8.0, 37°C, purified recombinant mutant p51-G-TCR construct
0.00019
beta-thujaplicinol
Human immunodeficiency virus 1
-
mutant enzyme Q475A, at pH 7.8 and 37°C
0.00022
beta-thujaplicinol
Human immunodeficiency virus 1
-
mutant enzyme R557A, at pH 7.8 and 37°C
0.000257
beta-thujaplicinol
Human immunodeficiency virus 1
-
pH 8.0, 37°C, purified recombinant wild-type HIV-1 reverse transcriptase RNase H
0.0022
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
Human immunodeficiency virus 1
-
pH 7.6, 37°C
0.003
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
Human immunodeficiency virus 1
-
pH 7.6, 37°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
level of RNase H activity is low in HIV-2 isolates
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
51000
-
1 * 51000, p51 subunit, + 1 * 66000, p66 subunit, of HIV reverse transcriptase, SDS-PAGE
66000
-
1 * 51000, p51 subunit, + 1 * 66000, p66 subunit, of HIV reverse transcriptase, SDS-PAGE
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
-
1 * 71000, SDS-PAGE of recombinant enzyme with deletion of 204 nucleotides at the 3'-terminus
additional information
dimer
-
1 * 51000, p51 subunit, + 1 * 66000, p66 subunit, of HIV reverse transcriptase, SDS-PAGE
additional information
-
RNase H activity is associated with the p66 component of reverse transcriptase
additional information
-
the folded structure of the HIV-1 RNase H domain takes the form of a 5-stranded mixed beta-sheet flanked by four alpha helices in an asymmetric distribution, structure comparisons, overview. The p66 subunit is subdivided into three domains: the N-terminal polymerase domain, the C-terminal ribonuclease RNase H domain, and connection domain that links the two functional regions
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2.80 A and 2.04 A resolution crystal structures of inhibitor, beta-thujaplicinol, bound at the RNase H active site of both HIV-1 RT and an isolated RNase H domain. beta-Thujaplicinol chelates two divalent metal ions at the RNase H active site
-
crystal structure analysis, overview. The pyrimidinol carboxylic acids is successful crystallized with Mn2+ and the isolated HIV RNase H domain
-
docking simulation studies. Residue His 539 and two metal ions in the RNase H catalytic center are involved in inhibition by compounds 5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester and 5-nitrofuran-2-carboxylic acid [[4-(4-bromophenyl)-thiazol-2-yl]-(tetrahydrofuran-2-ylmethyl)-carbamoyl]-methyl ester
-
in complex with substrate, hanging drop vapor diffusion method, using 50 mM Bis-Tris propane-HCl pH 7.0, 10% PEG 8000 (w/v), 100 mM ammonium sulfate, 5% glycerol (v/v), 5% sucrose (w/v) and 20 mM MgCl2
-
isolated recombinant RNase H domain, to 2.4 A resolution. The protein folds into a five-stranded mixed beta sheet flanked by an asymmetric distribution of four alpha helices. Two divalent metal cations bind in the active site surrounded by a cluster of four conserved acidic amino acid residues. The peptide bond cleaved by HIV-1 protease near the polymerase-RNase H junction of polypeptide p66 is completely inaccessible to solvent in the structure reported here, suggesting that the homodimeric p66-p66 precursor of mature RT is asymmetric with one of the two RNase H domains at least partially unfolded
-
modeling of the kinetic refolding intermediate using a C-terminal deletion fragment lacking helix E. Like the kinetic intermediate, this variant folds rapidly and shows a decrease in stability
-
purified p66/p51 HIV-1 reverse transcriptase 52A variant in complex with inhibitors manicol and TMC278, 0.0012 ml of 20 mg/mL protein in 9.2 mM Tris, pH 8.0, 68.7 mM NaCl, 3.6 mM manganese sulfate, 0.7 mM tris(2-carboxyethyl) phosphine, 0.27% w/v, beta-ocytl glucopyranoside, 7% v/v DMSO, 0.9 mM manicol, and 0.7 mM TMC278, mixed with 0.0012 ml of reservoir solution containing 50 mM HEPES pH 7.5, 100 mM ammonium sulfate, 15 mM manganese sulfate, 10 mM spermine, 5 mM TCEP, and 11% w/w PEG 8000, X-ray diffraction structure determination and analysis at 2.7 A resolution, modeling
-
purified recombinant detagged enzyme, mixing of 8-10 mg/ml protein in 20 mM potassium phosphate, pH 7.0, and 1 mM inhibitor nevirapine, with reservoir buffer containing 100 mM sodium cacodylate, pH 6.8, and 800 mM sodium citrate, in a 1:1 ratio, X-ray diffraction structure determination and analysis. Isolated RNase H domain is crystallized in a buffer containing 100 mM sodium citrate, pH 5.0, and 15 to 20% PEG-8000. Crystals are harvested for inhibitor soaking in the reservoir solution with the addition of 50 mM MnCl2, and 1 mM inhibitor nevirapine, at 4°C. Mn2+ is used as a surrogate for Mg2+ since soaking experiments with Mg2+ cannot reproducibly yield structures with inhibitor bound
purified wild-type enzyme in complex with polypurine tract RNA:DNA oligonucleotide, hanging drop vapour diffusion method, mixing of equal volumes of protein and precipitant solution, the latter contains 100 mM cacodylate, pH 5.6, 29-31% saturated ammonium sulfate, 4°C, X-ray diffraction structure determination and analysis at 3.0 A resolution, molecular replacement
solution structural dynamics. Enzyme is an asymmetric heterodimer of two subunits, p66 and p51. The two subunits have the same N-terminal sequence, with the p51 subunit lacking the C-terminal RNase H domain. The p66 subunit contains the polymerase and RNase H catalytic sites. H/D exchange indicates that the RNase H domain of p66 is very flexible
-
study on dynamics of RT in unliganded and inhibitor-bound forms by structure-based approach. Non-nucleoside RT inhibitors such as nevirapine interfere directly with the global hinge-bending mechanism that controls the cooperative motions of the p66 fingers and thumb subdomains. The net effect of nevirapine binding is to change the direction of domain movements rather than suppress their mobilities. The second generation non-nucleoside reverse transcriptase inhibitor, efavirenz, on the other hand, shows the stronger effect of simultaneously reorienting domain motions and obstructing the p66 thumb fluctuations. A second hinge site controlling the global rotational reorientations of the RNase H domain is identified
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29.7
-
melting temperature, mutant H638G; melting temperature, wild-type
43.5
-
melting temperature, mutant H638G, presence of 1 mM Mn2+
43.6
-
wild-type, 50% residual activity after a 10 min incubation
46.2
-
wild-type, 50% residual activity after a 10 min incubation, presence of primer-template
46.3
-
melting temperature, mutant D524N, presence of 1 mM Mn2+
46.9
-
melting temperature, mutant D653N, presence of 1 mM Mn2+
47.3
-
mutant D524A, 50% residual activity after a 10 min incubation
48.4
-
melting temperature, mutant D583N, presence of 1 mM Mn2+
48.8
-
melting temperature, mutant E562Q, presence of 1 mM Mn2+
49.7
-
mutant D524A, 50% residual activity after a 10 min incubation, presence of primer-template
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a HIV-1 RNase H specific inhibitor from the hydroxyimide class, that contains a primary amine with a long nonfunctional linker, is conjugated to NHS-activated HiTrap HP resins for use in affinity chromatographic HIV reverse transcriptase purifcation. Purification of untagged HIV-1 RT using an avidin affinity column in presence of Mg2+, method evaluations, overview
-
HiTrap column chromatography and Superdex 200 gel filtration
-
Ni-NTA column chromatography and heparin column chromatography
-
recombinant His-tagged enzyme by nickel affinity chromatography, the His6 tag is removed by proteolysis with thrombin, followed by gel filtration
recombinant His-tagged p66 or p51 HIV-1 RT DNA fragment from Escherichia coli strain BL21(DE3)pLys by nickel affinity chromatography, expression of a heterodimer of wild-type or F160S and C280S mutant p66 and p51 using plasmid vector RT69A in Escherichia coli strain Rosetta
-
recombinant His6-tagged p66/p51 HIV-1 reverse transcriptase 52A variant C280S by nickel affinity chromatography, the tag is cleaved by HRV14 3C protease
-
soluble recombinant RNase H, in an N-terminally His-tagged construct, p51-G-TCR construct, designed to encode the p51 subunit joined by a linker to the thumb (T), connection (C), and RNase H (R) domains of p66, from Escherichia coli strain MIC2067(DE3) by nickel affinity chromatography
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning a His-tagged p66 or p51 HIV-1 RT DNA fragment into the pQE-9 vector and expression in Escherichia coli strain BL21(DE3)pLys
-
expression in Escherichia coli
expression of His6-tagged p66/p51 HIV-1 reverse transcriptase p51/p66 52A variant C280S, the p66 subunit also contains the mutations K172A and K173A
-
expression of RNase H domain from residue Y427 to L560 as fusion protein in Escherichia coli
-
expression of RNase H, in an N-terminally His-tagged construct designed to encode the p51 subunit joined by a linker to the thumb (T), connection (C), and RNase H (R) domains of p66, in Escherichia coli strain MIC2067(DE3) lacking endogenous RNase HI and HII as soluble protein. The construct G provides sufficient RNase H activity to complement Escherichia coli growth at 42°C
-
expression of the isolated RNase H domain in Escherichia coli
-
isolated 125-residue RNase H domain consisiting of residues G436-L560 of polypepitde p6
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D549A
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mutation in polypeptide p66, decrease in RNase H activity
D549N
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mutation in polypeptide p66, decrease in RNase H activity
E478Q
A360I
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
A360I/V
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site-directed mutagenesis, a connection/RNase H domain mutant
A360K
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
A360V
A371V
A376S
A554K
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
A554L
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
A554T
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
C280P
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significant reduction in RNase H activity. A heterodimer p66C280p/p51C280P shows about 8% of wild-type RNaseH activity, 6% of strand transfer activity, and 105% of DNA polymerase activity. A heterodimer p66C280P/p51 shows about 60% of wild-type RNaseH activity, 80% of strand transfer activity, and 100% of DNA polymerase activity. A heterodimer p66/p51C280W shows about 30% of wild-type RNaseH activity, 6% of strand transfer activity, and 99% of DNA polymerase activity
C280S
C280S/K172A/K173A
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p66/p51 HIV-1 reverse transcriptase 52A mutant variant, the mutation C208S resides in both subunits, the p66 subunit also contains the mutations K172A and K173A
C280W
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significant reduction in RNase H activity. A heterodimer p66C280W/p51C280W shows about 11% of wild-type RNaseH activity, 6% of strand transfer activity, and 100% of DNA polymerase activity. A heterodimer p66C280W/p51 shows about 44% of wild-type RNaseH activity, 80% of strand transfer activity, and 98% of DNA polymerase activity. A heterodimer p66/p51C280W shows about 29% of wild-type RNaseH activity, 7% of strand transfer activity, and 100% of DNA polymerase activity
D549N
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mutation increases the 3'-azido-3'-deoxythymidine concentration needed to inhibit viral replication by 50% 12fold by increasing the time available for excision of incorporated nucleoside reverse transcriptase inhibitors from terminated primers and results in 5- to 10fold reduction in viral titers in a single-replication cycle assay
D67N
E312Q
E396A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
E475A
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site-directed mutagenesis, the mutant shows only minimally altered substrate specificity or enzyme activity compared to the wild-type enzyme. But the efficiency with which most mutants catalyzed polymerization-independent RNase H cleavage is sharply reduced. This deficiency is more pronounced when the mutant enzyme is challenged to process the (+) strand polypurine tract (PPT) primer from either (+) RNA or a PPT/(+) DNA RNA/DNA chimera
E478Q
E478Q/N348I
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mutation of RNase H active site and connection domain
E706Q
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site-directed mutagenesis of HIV-1 reverse transcriptase, inactive mutant; site-directed mutagenesis of the recombinant mutant construct G, E706 in construct G corresponds to E478 in HIV-1 reverse transcriptase, inactive mutant
F227L
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
G190A
G190S
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site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
G333E
G335C
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
G335D
G359A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
G509L
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Glu to Leu substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance, mechanism, overview. Q509L increases zidovudine monophosphate excision activity of RT on RNA/DNA template/primers, but not DNA/DNA template/primers, due to Q509L decreasing a secondary RNase H cleavage event that reduces the RNA/DNA duplex length to 10 nucleotides and significantly impairs the enzyme's ability to excise the chain-terminating nucleotide. Mutation Q509L does not affect initial rates of the polymerase-directed RNase H activity but only polymerase-independent cleavages that occur after a template/primer dissociation event. Q509L decreases the affinity of the enzyme to bind template/primers with duplex lengths less than 18 nucleotides in the polymerase-independent RNase H cleavage mode, while not affecting the enzyme's affinity to bind the same template/primers in an zidovudine monophosphate excision competent mode
G544Stop
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C-terminal truncation of p66 polypeptide. Loss of RNase H activity, while dimerization with polypepitde p51 and DNA polymerase activity are not significantly affected
H539F
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mutation in isolated RNase H domain, mutant fails to bind RNA/DNA hybrids. Structure of mutant is similar to wild-type
H539N
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increases the 3'-azido-3'-deoxythymidine concentration needed to inhibit viral replication by 50% 180fold relative to wild-type by increasing the time available for excision of incorporated nucleoside reverse transcriptase inhibitors from terminated primers
I505A
I505G
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site-directed mutagenesis, the mutant exhibits a dimerization defect. The efficiency with which most mutants catalyzed polymerization-independent RNase H cleavage is sharply reduced. This deficiency is more pronounced when the mutant enzyme is challenged to process the (+) strand polypurine tract (PPT) primer from either (+) RNA or a PPT/(+) DNA RNA/DNA chimera
K103N
K219E
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
K219N
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
K219Q
K390A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K395A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K451R
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mutation present in viral isolates of 11% of antiviral treatment-experienced patients but remaining 100% conserved among treatment-naive patients
K476A
K558E
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, associated with an increase in thymidine analogue mutations, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
K558G
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, associated with an increase in thymidine analogue mutations, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
K558R
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, associated with an increase in thymidine analogue mutations, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
K65R
K65R/Q151M/A62V/V75I/F77L/F116Y
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
K70R
L100I
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
L210W
L469H
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
L469I
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
L469M
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
L469T
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
L74V
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
M184V
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naturally occuring mutation in HIV infection patients, arises with abacavir, emtricitabine, or lamivudine treatment
M230L
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the naturally occuring mutation leads to reduced RNase H activity of the HIV reverse transcriptase
M41L
N348I
N474A
N474A/Q475A
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mutation reduces the viral titer 5- to 10fold, , reduction in the efficiency of DNA synthesis. Mutant is less efficient than the wild-type enzyme in its ability to remove a polypurine tract primer from a model substrate and has an altered RNase H cleavage specificity
N494D
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mutant closely resembles the wild-type RNase H, exhibits an endonuclease activity and a processive RNase H activity, gives rise to small RNA hydrolysis products, and acts in concert with the reverse transcriptase
P236L
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site-directed mutagenesis, the mutant virus shows substantially reduced fitness compared to that of the wild-type virus
P537Stop
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C-terminal truncation of p66 polypeptide. Loss of RNase H activity, while dimerization with polypepitde p51 and DNA polymerase activity are not significantly affected
Q151M
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
Q151M/A62V/V75I/F77L/F116Y
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
Q475A
Q475E
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mutant exhibits a retarded endonuclease activity and an impaired 3'-5' processive RNA cleavage activity, gives rise to predominantly larger RNA hydrolysis products, is less processive in the presence of competitor substrate, and is defective in its ability to hydrolyze the polypurine tract and homopolymeric hybrids
Q509L
R448A
R557A
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the mutant shows about 5fold reduced kcat value compared to the wild type enzyme
T215F
T215Y
T470E
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
T470K
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
T470P
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
T470S
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naturally occuring mutation in HIV infection patients, the mutation renders the patient more prevalent amongst treatment-experienced patients, treatment with nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors
T473A
T473C
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the mutation increases the sensitivity of the enzyme for inhibitor NSC727447 by 50fold
T473M
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
V106A
V365I
V552Stop
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C-terminal truncation of p66 polypeptide. Mutant retains endonuclease activity but lacks the directional processing feature of wild-type and barely supports transfer of nascent (-)-stranded DNA between RNA templates
W229F
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mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
W229F/Y232W
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mutation in primer grip residues, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
W229Y
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mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
Y181C
Y188C
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
Y188L
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
Y229F/Y232F
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mutation in primer grip residues, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
Y232W
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mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
Y501A
E478Q/N348I
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mutation of RNase H active site and connection domain
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N348I
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connection domain mutant, altered RNase H cleavage pattern compared to the wild-type HIV-1 RT
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E396A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
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K390A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
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K395A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
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K65R
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naturally occuring mutation in HIV infection patients, arises with abacavir, didanosine, emtricitabine, lamivudine, or tenofovir disoproxil fumarate treatment
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M230L
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the naturally occuring mutation leads to reduced RNase H activity of the HIV reverse transcriptase
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Y501A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
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Q294P
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site-directed mutagenesis of a residue in the catalytically inactive p54 subunit resulting in an increase in RNase H activity comparable with that of HIV-1 reverse transcriptase
A128T
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the mutant strain is resistant to 2-hydroxyisoquinoline-1,3(2H,4H)-dione inhibitors in contrast to the wild-type
C635V
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site-directed mutagenesis, the mutant shows slightly reduced reverse transcriptase and RNAse H activities compared the wild-type enzyme
D524A
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mutant lacks RNase H activity, but retains reverse transcriptase activity. Elimination of RNase H activity enhances the intrinsic thermal stability of the protein rather than its affinity to template-primer; site-directed mutagenesis, RNase H-inactive mutant, that shows increased intrinsic thermal stability compared to the wild-type enzyme. The mutant loses RNase H activity through abolishing of Mg2+ binding to the RNase H domain
D524N
D583A
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site-directed mutagenesis, RNase H-inactive mutant, that shows increased intrinsic thermal stability compared to the wild-type enzyme. The mutant loses RNase H activity through abolishing of Mg2+ binding to the RNase H domain
D583N
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less than 0.5% of wild-type activity, no binding of Mn2+
E562Q
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less than 0.5% of wild-type activity, no binding of Mn2+
G140S/Q148H
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the mutant strain is resistant to 2-hydroxyisoquinoline-1,3(2H,4H)-dione inhibitors in contrast to the wild-type
D358N
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mutation eliminates Mg2+- and Mn2+-dependent RNase H function
D426N
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mutation eliminates Mg2+- and Mn2+-dependent RNase H function
D469N
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reduced RNase H activity in presence of Mg2+, decrease of turnover rate in presence of Mn2+. Mutant fails to support DNA strand transfer and release of the (+)-strand polypurine tract primer from (+)-RNA
E401Q
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mutation eliminates Mg2+- and Mn2+-dependent RNase H function
H427A
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reduced RNase H activity in presence of Mg2+, decrease of turnover rate in presence of Mn2+. Mutant fails to support DNA strand transfer and release of the (+)-strand polypurine tract primer from (+)-RNA
Y459A
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reduced RNase H activity in presence of Mg2+, decrease of turnover rate in presence of Mn2+. Mutant fails to support DNA strand transfer and release of the (+)-strand polypurine tract primer from (+)-RNA
additional information
E478Q
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the efficiency with which mutant RT catalyzes transfer of nascent DNA between RNA templates is severely reduced
A360V
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
A360V
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naturally occuring mutant from clinical isolates, a connection/RNase H domain mutant that shows reduced RNase H activity
A371V
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B, whereas the G335D and A371V substitutions are commonly observed in 69% and 75% of non-B HIV-1 isolates, respectively
A371V
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site-directed mutagenesis, a connection/RNase H domain mutant
A376S
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B. Mutations N348I, A376S and Q509L do confer varying amounts of nevirapine resistance by themselves, even in the absence of excision-enhancing mutations
A376S
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
D67N
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
E312Q
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B
E312Q
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
E478Q
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mutation in isolated RNase H domain, mutant fails to bind RNA/DNA hybrids. Structure of mutant is similar to wild-type
G190A
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site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
G190A
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
G333E
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B
G335D
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B, whereas the G335D and A371V substitutions are commonly observed in 69% and 75% of non-B HIV-1 isolates, respectively
G335D
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
I505A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K103N
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site-directed mutagenesis, the mutation does not affect RNase H function
K103N
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site-directed mutagenesis, the mutant virus shows fitness similar to that of the wild-type virus
K103N
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
K219Q
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
K476A
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site-directed mutagenesis, the mutant shows only minimally altered substrate specificity or enzyme activity compared to the wild-type enzyme. But the efficiency with which most mutants catalyzed polymerization-independent RNase H cleavage is sharply reduced. This deficiency is more pronounced when the mutant enzyme is challenged to process the (+) strand polypurine tract (PPT) primer from either (+) RNA or a PPT/(+) DNA RNA/DNA chimera
K476A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K65R
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naturally occuring mutation in HIV infection patients, arises with abacavir, didanosine, emtricitabine, lamivudine, or tenofovir disoproxil fumarate treatment
K65R
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
K70R
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naturally occuring mutation in HIV infection patients, is common to stavudine, tenofovir disoproxil fumarate, and zidovudine therapy; thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
L210W
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-1 pathway
M41L
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-1 pathway
N348I
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mutations N348I, A376S and Q509L do confer varying amounts of nevirapine resistance by themselves, even in the absence of excision-enhancing mutations
N348I
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connection domain mutant, altered RNase H cleavage pattern compared to the wild-type HIV-1 RT
N348I
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
N348I
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naturally occuring mutant from clinical isolates, a connection/RNase H domain mutant that shows reduced RNase H activity
N474A
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the mutant shows about 40fold reduced kcat value compared to the wild type enzyme
Q475A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
Q475A
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the mutant shows about 10fold reduced kcat value compared to the wild type enzyme
Q509L
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mutations N348I, A376S and Q509L do confer varying amounts of nevirapine resistance by themselves, even in the absence of excision-enhancing mutations
Q509L
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mutation in the RNase H domain, the mutation significantly contributes to zidovudine resistance
Q509L
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site-directed mutagenesis, a connection/RNase H domain mutant
R448A
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the mutant shows about 3fold reduced kcat value compared to the wild type enzyme
T215F
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
T215Y
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thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-1 pathway
T473A
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site-directed mutagenesis, the mutant shows only minimally altered substrate specificity or enzyme activity compared to the wild-type enzyme. But the efficiency with which most mutants catalyzed polymerization-independent RNase H cleavage is sharply reduced. This deficiency is more pronounced when the mutant enzyme is challenged to process the (+) strand polypurine tract (PPT) primer from either (+) RNA or a PPT/(+) DNA RNA/DNA chimera
V106A
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site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
V106A
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
V365I
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B
V365I
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mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
Y181C
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site-directed mutagenesis, the mutation does not affect RNase H function
Y181C
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site-directed mutagenesis, the mutant virus shows fitness similar to that of the wild-type virus
Y181C
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
Y181C
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site-directed mutagenesis, the mutant shows resistance to non-nucleoside reverse transcriptase inhibitors
Y501A
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site-directed mutagenesis, the mutant shows only minimally altered substrate specificity or enzyme activity compared to the wild-type enzyme. But the efficiency with which most mutants catalyzed polymerization-independent RNase H cleavage is sharply reduced. This deficiency is more pronounced when the mutant enzyme is challenged to process the (+) strand polypurine tract (PPT) primer from either (+) RNA or a PPT/(+) DNA RNA/DNA chimera
Y501A
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mutation reduces the viral titer 5- to 10fold, reduction in the efficiency of DNA synthesis. Mutant is less efficient than the wild-type enzyme in its ability to remove a polypurine tract primer from a model substrate and has an altered RNase H cleavage specificity
Y501A
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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
Y501A
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the mutant shows about 400fold reduced kcat valuecompared to the wild type enzyme
D524N
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loss of catalytic activity. Construction of vectors encapsidated in virions engineered to contain phenotypic mixtures of wild-type and RNase H catalytic site point mutant D524N reverse transcriptase. There is a steady decline in direct repeat deletion frequency that correlates with decreases in functional RNase H, with greater than fourfold decreases in repeat deletion frequency observed when 95% of virion reverse transcriptase is RNase H defective
D524N
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less than 0.5% of wild-type activity, no binding of Mn2+
additional information
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RNase H primer grip mutations suppress polymerization-independent RNase H cleavage. Alteration of RNase H primer grip residues Thr473, Asn474, and Gln475 has little influence on cleavage specificity. Altering the RNase H domain of HIV-1 RT can impact significantly on the ability of mutant enzymes to catalyze DNA synthesis, but all RNase H primer grip mutants show little difference in their DNA-dependent DNA polymerase activity
additional information
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construction of chimeric HIV-1/HIV-2 reverse transcriptases, in which protein segments and/or subunits are exchanged. The RNase H specific activity of the chimeric enzymes is either high like HIV-1 reverse transcriptase or low like HIV-2 reverse transcriptase. The origin of the thumb subdomain in the small subunit of the chimeric reverse transcriptases, residues 244-322 determines the level of the RNase H activity
additional information
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chemical modifications by thiol-specific reagents of cysteine 280, located in a helix I in the thumb subdomain of the polymerase domain, affect substantially only the RNase H activity
additional information
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construction of two chimeric enzymes by swapping the RNase H domains between HIV-1 RT and Moloney murine leukemia virus MuLV RT. Chimeric HIV-1 RT, having the RNase H domain of MuLV RT, inherits the divalent cation preference characteristic of MuLV RT on the DNA template with no significant change on the RNA template. Chimeric MuLV RT, likewise partially inherits the metal ion preference of HIV-1 RT. Unlike the wild-type MuLV RT, chimeric MuLV RT is able to use both Mn-dNTP and Mg-dNTP on the RNA template with similar efficiency, while a 30-fold higher preference for Mn.dNTP was seen on the DNA template. The metal preferences for the RNase H activity of chimeric HIV-1 RT and chimeric MuLV RT are, respectively, Mn2+ and Mg2+, a property acquired through their swapped RNase H domains. Chimeric HIV-1 RT displays higher fidelity and discrimination against rNTPs than against dNTPs substrates, a property inherited from MuLV RT. The overall fidelity of the chimeric MuLV RT is decreased in comparison to the parental MuLV RT, suggesting that the RNase H domain profoundly influences the function of the polymerase domain
additional information
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construction of an N-terminally His-tagged mutant p51-G-TCR construct designed to encode the p51 subunit joined by a linker to the thumb (T), connection (C), and RNase H (R) domains of p66, the p51-G-TCR RNase H construct displays Mg2+-dependent activity using a fluorescent nonspecific assay and shows the same cleavage pattern as HIV-1 reverse transcriptase on substrates that mimic the tRNA removal required for second-strand transfer reactions. The RNase H of the p51-G-TCR RNase H construct and wild-type HIV-1 reverse transcriptase have similar Kms for an RNA-DNA hybrid substrate and show similar inhibition kinetics to two known inhibitors of the HIV-1 reverse transcriptase RNase H, molecular modeling
additional information
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construction of chimeric HIV-1/HIV-2 reverse transcriptases, in which protein segments and/or subunits are exchanged. The RNase H specific activity of the chimeric enzymes is either high like HIV-1 reverse transcriptase or low like HIV-2 reverse transcriptase. The origin of the thumb subdomain in the small subunit of the chimeric reverse transcriptases, residues 244-322 determines the level of the RNase H activity
additional information
-
construction of chimeric HIV-1/HIV-2 reverse transcriptases, in which protein segments and/or subunits are exchanged. The RNase H specific activity of the chimeric enzymes is either high like HIV-1 reverse transcriptase or low like HIV-2 reverse transcriptase. The origin of the thumb subdomain in the small subunit of the chimeric reverse transcriptases, residues 244-322 determines the level of the RNase H activity
-
additional information
-
construction of chimeric HIV-1/HIV-2 reverse transcriptases, in which protein segments and/or subunits are exchanged. The RNase H specific activity of the chimeric enzymes is either high like HIV-1 reverse transcriptase or low like HIV-2 reverse transcriptase. The origin of the thumb subdomain in the small subunit of the chimeric reverse transcriptases, residues 244-322 determines the level of the RNase H activity
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additional information
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deletion of 204 nucleotides at the 3'-terminus results in 4fold increase in activity level upon recombinant expression and allows for high-level production of the protein
additional information
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construction of two chimeric enzymes by swapping the RNase H domains between HIV-1 RT and Moloney murine leukemia virus MuLV RT. Chimeric HIV-1 RT, having the RNase H domain of MuLV RT, inherits the divalent cation preference characteristic of MuLV RT on the DNA template with no significant change on the RNA template. Chimeric MuLV RT, likewise partially inherits the metal ion preference of HIV-1 RT. Unlike the wild-type MuLV RT, chimeric MuLV RT is able to use both Mn-dNTP and Mg-dNTP on the RNA template with similar efficiency, while a 30-fold higher preference for Mn.dNTP was seen on the DNA template. The metal preferences for the RNase H activity of chimeric HIV-1 RT and chimeric MuLV RT are, respectively, Mn2+ and Mg2+, a property acquired through their swapped RNase H domains. Chimeric HIV-1 RT displays higher fidelity and discrimination against rNTPs than against dNTPs substrates, a property inherited from MuLV RT. The overall fidelity of the chimeric MuLV RT is decreased in comparison to the parental MuLV RT, suggesting that the RNase H domain profoundly influences the function of the polymerase domain
additional information
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site-directed chemical modification of the RNase H domain by selectively PEGylating Cys635, one of the eight cysteine residues present in the reverse transcriptase, specifically inactivates its ribonucleolytic activity, PEGylation as a tool for engineering the M-MuLV RT derivative deficient in RNase H activity, overview
additional information
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construction of a chimeric enzyme containing the first 425 amino acid residues from the N-terminal domain of HIV-1 reverse transcriptase, i.e. the polymerase domain, and 200 amino acid residues from the C-terminal domain of murine leukemia virus reverse transcriptase, i.e. RNase H-domain. The chimeric enzyme exists as a monomer with intact DNA polymerase and RNase-H functions. It is able to catalyze both endonucleolytic and processive RNase-H functions in a manner similar to the wild type HIV-1 reverse transcriptase and murineleukemia virus reverse transcriptase
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Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Refolding of the isolated HIV RNase H domain shows a kinetic intermediate detectable by stopped-flow far UV circular dichroism and pulse-labeling H/D exchange. In this intermediate, strands 1, 4, and 5 as well as helices A and D appear to be structured. Compared to its homolog from Escherichia coli, the rate limiting step in refolding of HIV RNase H appears closer to the native state. This kinetic intermediate has been modeled using a C-terminal deletion fragment lacking helix E. Like the kinetic intermediate, this variant folds rapidly and shows a decrease in stability
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
drug development
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RNase H activity is an attractive target for a new class of antiviral drugs
medicine
pharmacology
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mutations in RNase H can significantly contribute to drug resistance either alone or in combination with nucleoside reverse transcriptase inhibitor-resistance mutations in reverse transcriptase. There exists an equilibrium between nucleoside reverse transcriptase inhibitor incorporation, nucleoside reverse transcriptase inhibitor excision, and resumption of DNA synthesis and degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication
analysis
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use of a commercially available computed radiography system for dental radiography to produce images from radiolabeled polyacrylamide gel electrophoresis assays and its application for quantitative analyses of the human immunodeficiency virus type 1 reverse transcriptase polymerase-independent ribonuclease H activity monitored by PAGE analysis. The methodology allows quantifying effectively the RNase H catalyses and the obtained data are in good agreement with previous reference works
analysis
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use of 6-phenylpyrrolocytidine as a sensitive fluorescent reporter group being non-disruptive to structure and the enzymatic activity of RNase H. A RNA/DNA hybrid possessing a single 6-phenylpyrrolocytidine insert is an excellent substrate for HIV-1 RT Ribonuclease H and rapidly reports cleavage of the RNA strand with a 14-fold increase in fluorescence intensity. The 6-phenylpyrrolocytidine-based assay for RNase H is superior to the traditional molecular beacon approach in terms of responsiveness, rapidity and ease. The assay is amenable to high-throughput microplate assay format
medicine
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genotypical and statistical analyzes in HIV-1 reverse transcriptase from antiretroviral treatment-naive and antiretroviral treatment-experienced patients. Within the RNase H domain, change K451 is present in 11% of treatment-experienced patients, but not in treatment-naive patients; within the RNase domain, mutation K451R is present in viral isolates of 11% of antiviral treatment-experienced patients but remaining 100% conserved among treatment-naive patients
medicine
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the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B, whereas the G335D and A371V substitutions are commonly observed in 69% and 75% of non-B HIV-1 isolates, respectively. A significant decline is observed in the viral loads of patients that are infected with HIV-1 carrying these substitutions and are subsequently treated with triple drug regimens, even in the case where zidovudine is included in such regimens. Generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance zidovudine resistance in the presence of excision-enhancing mutations. However, N348I, A376S and Q509L do confer varying amounts of nevirapine resistance by themselves, even in the absence of excision-enhancing mutations
medicine
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activating the RNase H prematurely inside the virus particles destroys the viral genome and abrogates viral infectivity
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