Information on EC 3.1.26.13 - retroviral ribonuclease H

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.1.26.13
-
RECOMMENDED NAME
GeneOntology No.
retroviral ribonuclease H
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REACTION
REACTION DIAGRAM
COMMENTARY hide
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.
show the reaction diagram
CAS REGISTRY NUMBER
COMMENTARY hide
9050-76-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
HIV-1
-
-
Manually annotated by BRENDA team
strain D-194, low level of RNase H activity
-
-
Manually annotated by BRENDA team
strain ROD, low level of RNase H activity
-
-
Manually annotated by BRENDA team
retrotransposon Ty3, gypsy-group
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5'-end-labeled 267 nt-long RNA annealed to 20 nt-long synthetic DNA + H2O
?
show the reaction diagram
-
-
-
-
?
5'-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC-dGdGdGdGdAdTdCdCdTdCdTdAdG-3'/3'-dTdCdGdAdGdCdCdAdTdGdGdG-dCdCdCdCdTdAdGdGdAdGdTdC-5' + H2O
5'-rGrGrGrCrGrArArUrUrCrGrArGrCrUrCrGrGrUrArCrCrC/dGdGdGdGdAdTdCdCdTdCdTdAdG-3' + 3'-dTdCdGdAdGdCdCdAdTdGdGdG/dCdCdCdCdTdAdGdGdAdGdTdC-5'
show the reaction diagram
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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'
show the reaction diagram
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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
?
show the reaction diagram
5-rGrGrGrUrCrCrCrUrGrUrUrCrGrGrGrCrGrCrCrA-dCdTdGdCdTdAdGdAdGdAdTdTdTdTdT-3 + 3-dGdAdCdAdAdGdCdCdCdGdCdGdGdT-dGdAdCdGdAdTdCdTdCdTdAdAdAdAdA-5 + H2O
?
show the reaction diagram
DNA-RNA/DNA hybrid + H2O
?
show the reaction diagram
-
-
-
-
?
poly(A)+ mRNA primed with oligo(dT) + H2O
double-stranded DNA copies between 1.3 and 9.9 kilobases in length + ?
show the reaction diagram
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multifunctional enzyme containing RNase H and reverse transcriptase activity
-
-
?
poly(dC)-poly(rG) + H2O
?
show the reaction diagram
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-
-
-
?
poly(dT)-poly(rA) + H2O
?
show the reaction diagram
-
substrate poly(dC)-poly(rG) is markedly preferred over substrate poly(dT)-poly(rA)
-
-
?
poly(rA)/oligo(dT)+ H2O
?
show the reaction diagram
-
synthetic hybrid
-
-
?
poly(rA)n-poly(dT)n + H2O
?
show the reaction diagram
-
-
-
-
?
poly(rG)/poly(dC) + H2O
?
show the reaction diagram
RNA-DNA duplex + H2O
?
show the reaction diagram
-
-
-
-
?
RNA-DNA hybrid + H2O
?
show the reaction diagram
RNA-DNA hybrid containing the polypurine tract + H2O
?
show the reaction diagram
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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
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-
?
RNA:DNA hybrid + H2O
AMP + ?
show the reaction diagram
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-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
RNA-DNA duplex + H2O
?
show the reaction diagram
-
-
-
-
?
RNA-DNA hybrid + H2O
?
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
Ca2+ is non-competent analogue of the Mg2+ ion cofactor
KCl
-
optimum concentration 50 mM
Zn2+
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optimal RT RNase H activity at about 0.025 mM Zn2+
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
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(5E)-6-[1-(3-methoxybenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
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(5E)-6-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxohex-5-enoic acid
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-
(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
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-
1,2-bis(2-oxopropoxy)anthracene-9,10-dione
-
9% inhibition
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
1,3,4,5-tetrahydrogalloylapitol
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-
1,6,8-trihydroxy-3-methylanthraquinone
-
i.e. frangula-emodin
1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine
-
-
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
1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one
-
-
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-(propan-2-yl)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-(3,4-dichlorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
2-(3-bromo-4-methoxybenzyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
-
inhibition of enzymatic activity, but no antiviral effect
2-(tert-butylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
2-amino-2-oxoethyl 5-nitrofuran-2-carboxylate
-
-
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-ethylisoquinoline-1,3(2H,4H)-dione
-
-
2-hydroxy-4-isopropylisoquinoline-1,3(2H,4H)-dione
-
-
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-hydroxy-4-methylisoquinoline-1,3(2H,4H)-dione
2-hydroxy-4-pentylisoquinoline-1,3(2H,4H)-dione
-
-
2-hydroxy-4-propylisoquinoline-1,3(2H,4H)-dione
-
-
2-hydroxyisoquinoline-1,3(2H,4H)-dione
2-hydroxyisoquinoline-1,3(2H,4H)-dione magnesium complex
-
-
-
2-oxo-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl 5-nitrofuran-2-carboxylate
-
-
2-oxo-2-(phenylamino)ethyl dibenzylcarbamodithioate
-
-
2-oxo-2-(propan-2-yloxy)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
-
-
3,3-dimethyl-2-oxobutyl 5-nitrofuran-2-carboxylate
-
-
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-([[4-benzyl-5-(thiophen-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-heptyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
-
enol form
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-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acid
-
-
4-[5-(benzoylamino)thiophen-2-yl]-2,4-dioxobutanoic acid
-
-
4-[[(4-fluorophenyl)methyl]amino]-1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one hydrobromide
-
-
-
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 adamantan-1-carbamoyl methyl ester
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
-
8-hydroxy-1,6-naphthyridine-7-carboxylic acid
-
-
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
9,10-dioxo-9,10-dihydroanthracene-1,2-diyl dibenzoate
-
-
Abacavir
actinomycin D
-
limits the enzyme to the first strand synthesis
beta-thujaplicinol
bis[3-(phosphonatooxy)propyl] phosphate
-
-
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
-
didanosine
dihydroxybenzoyl naphthyl hydrazone
-
-
efavirenz
Emtricitabine
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
-
-
ethyl 1,4-dihydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate
Etravirine
F3284-8495
-
specific inhibitor with low micromolar potency in vitro
GSK5750
-
active site inhibitor
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
lamivudine
methyl 2-hydroxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
-
-
Mn2+
-
activation at 0.01-1 mM, inhibitory above
N-(4-chlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide
-
-
nevirapine
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
-
pyrimidinol carboxylic acid
-
-
-
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
-
69% inhibition of RNase H at 0.05 microM
-
stavudine
tenofovir disoproxil fumarate
-
a nucleoside reverse transcriptase inhibitor
-
tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one
-
-
xylan polysulfate
-
more potent inhibitor of RNase H than of reverse transcriptase. 50% infective dose corresponds to 8 nM
-
zalcitabine
-
a nucleoside reverse transcriptase inhibitor
-
zidovudine
-
a nucleoside reverse transcriptase inhibitor
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
-
activates, effect on kinetics, overview
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.0663
poly(rA)n-poly(dT)n
0.000029 - 0.000126
RNA-DNA hybrid
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.024 - 0.034
poly(rA)n-poly(dT)n
0.004 - 1.9
RNA-DNA hybrid
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
510 - 10300
poly(rA)n-poly(dT)n
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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, 37C
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 37C
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 37C
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 37C
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 37C
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 37C
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 37C
0.075
1,6,8-trihydroxy-3-methylanthraquinone
Human immunodeficiency virus 1
-
-
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 22C
-
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 22C
-
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 22C
-
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 22C
-
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 22C
-
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 22C
-
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 22C
-
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, 37C
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, 37C
0.0061
2-(2,3-dihydro-1H-inden-1-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0055
2-(2,3-dihydro-1H-inden-2-ylamino)-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
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, 37C
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, 37C
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, 37C
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, 37C
0.0071
2-amino-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
0.08
2-hydroxy-4-(4-methylbenzyl)isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0427
2-hydroxy-4-(4-trifluoromethylbenzyl)isoquinoline-1,3(2H-4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0132
2-hydroxy-4-butylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0388
2-hydroxy-4-ethylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0185
2-hydroxy-4-isopropylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.000061
2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H, 4H)-dione
0.0388 - 0.07
2-hydroxy-4-methylisoquinoline-1,3(2H,4H)-dione
0.0336
2-hydroxy-4-pentylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0468
2-hydroxy-4-propylisoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.00012 - 0.0591
2-hydroxyisoquinoline-1,3(2H,4H)-dione
0.0301
2-hydroxyisoquinoline-1,3(2H,4H)-dione magnesium complex
Moloney murine leukemia virus
-
pH 8.0, 37C
-
0.0043
2-oxo-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
0.0042
2-oxo-2-(tetrahydrofuran-2-ylamino)ethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
0.0033
2-[(2,3,4-trichlorophenyl)amino]-2-oxoethyl dibenzylcarbamodithioate
Human immunodeficiency virus 1
-
pH 8.0, 25C
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, 25C; 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, 37C
0.0058
2-[(2-methylbutan-2-yl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
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, 37C
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, 25C; 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, 37C
0.0142
2-[tert-butyl(2-phenylethyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0098
2-[tert-butyl(3-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.05
2-[tert-butyl(3-oxo-3-phenylpropyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
0.0085
2-[tert-butyl(4-fluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0075
2-[tert-butyl(4-methoxybenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0069
2-[tert-butyl(4-nitrobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0068
2-[tert-butyl(pentafluorobenzyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0009
2-[tert-butyl(phenyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.009
2-[tert-butyl[2-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0085
2-[tert-butyl[3-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.008
2-[tert-butyl[4-(trifluoromethyl)benzyl]amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0128
2-[[2-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.0087
2-[[4-(acetyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
0.05
2-[[4-(benzyloxy)benzyl](tert-butyl)amino]-2-oxoethyl 5-nitrofuran-2-carboxylate
Human immunodeficiency virus 1
-
pH 7.5, 37C
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, 37C
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 22C
-
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 22C
-
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 22C
-
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 22C
-
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, 37C
0.0012
4-benzyl-3-(benzylsulfanyl)-5-(furan-2-yl)-4H-1,2,4-triazole
Human immunodeficiency virus 1
-
pH 8.0, 25C; 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, 25C; 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, 25C; 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, 25C; 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 - 0.0059
4-benzyl-3-[(4-methoxybenzyl)sulfanyl]-5-(thiophen-2-yl)-4H-1,2,4-triazole
0.045
4-heptyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
Human Immunodeficiency Virus
-
pH 8.0, 37C
0.0078 - 0.038
4-hexyl-2-hydroxy-isoquinoline-1,3(2H,4H)-dione
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 37C
-
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 37C
-
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 37C
-
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 37C
-
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 37C
-
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 37C
-
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 37C
-
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 hydrobromide
Human immunodeficiency virus 1
-
in 50 mM Tris, pH 8.0, 80 mM KCl, 10 mM MgCl2, at 22C
-
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, 37C
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, 37C
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, 37C
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, 37C
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, 37C
0.0038 - 0.0296
5-nitrofuran-2-carboxylic acid adamantan-1-carbamoyl methyl ester
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
0.000186 - 0.00047
ARK-2452
0.00007 - 0.0038
beta-thujaplicinol
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 37C
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 37C
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 37C
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 37C
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 37C
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 37C
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
0.0011 - 0.0048
F3284-8495
0.0019 - 0.0022
F3385-2581
0.0007 - 0.0021
F3385-2588
0.0004 - 0.0008
F3385-2590
0.00033
GSK5750
Human immunodeficiency virus 1
-
at pH 7.8 and 37C
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
-
-
-
0.0022 - 0.003
[2-(4-chlorophenyl)hydrazinylidene]propanedioic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
-
commercial preparation, pH 7.8, 37C
additional information
-
level of RNase H activity is low in HIV-2 isolates
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
virus passage in human 293 cells
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
71000
-
glycerol gradient centrifugation
110000
-
glycerol gradient centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 71000, SDS-PAGE of recombinant enzyme with deletion of 204 nucleotides at the 3'-terminus
additional information
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 4C. 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, 4C, 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
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29.7
-
melting temperature, mutant H638G; melting temperature, wild-type
29.9
-
melting temperature, wild-type, presence of 25 mM NaCl
34.1
-
melting temperature, wild-type, presence of 1 mM Mg2+
35.8
-
melting temperature, mutant E562Q
39.2
-
melting temperature, mutant D653N
42
-
melting temperature, wild-type, presence of 1 mM Mn2+
43.5
-
melting temperature, mutant H638G, presence of 1 mM Mn2+
43.6
-
wild-type, 50% residual activity after a 10 min incubation
45.8
-
melting temperature, mutant D524N
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+
48.9
-
melting temperature, mutant D583N
49.7
-
mutant D524A, 50% residual activity after a 10 min incubation, presence of primer-template
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 agarose column chromatography
-
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
-
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
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli XL1 Blue cells
-
expression in Escherichia coli
expression of His-tagged enzyme
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 42C
-
expression of the isolated RNase H domain in Escherichia coli
-
isolated 125-residue RNase H domain consisiting of residues G436-L560 of polypepitde p6
-
separate expression of subunits in Escherichia coli
-
transfection of HEK 293 cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D549A
-
mutation in polypeptide p66, decrease in RNase H activity
D549N
-
mutation in polypeptide p66, decrease in RNase H activity
A360I
-
mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
A360I/V
-
site-directed mutagenesis, a connection/RNase H domain mutant
A360K
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
A400T
-
mutation in the connection domain
A554K
-
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
-
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
-
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
C280E
-
RNase H activity similar to wild-type
C280H
-
RNase H activity similar to wild-type
C280L
-
RNase H activity similar to wild-type
C280M
-
RNase H activity similar to wild-type
C280P
-
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
C280Q
-
RNase H activity similar to wild-type
C280R
-
RNase H activity similar to wild-type
C280S/K172A/K173A
-
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
-
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
C280Y
-
RNase H activity similar to wild-type
D498N
-
active site mutant
D549N
-
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/K70R/T215F
-
site-directed mutagenesis
D67N/K70R/T215F/Q509L
-
site-directed mutagenesis
E396A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
E399D
-
mutation in the connection domain
E44A
-
mutation involved in lamivudine resistance
E44D
-
mutation involved in lamivudine resistance
E475A
-
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/N348I
-
mutation of RNase H active site and connection domain
E706Q
-
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
E89K
-
mutation involved in foscarnet resistance
F160S
-
site-directed mutagenesis
F227L
-
mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
G190S
-
site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
G333D
-
mutation in the connection domain
G335C
-
mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
G359A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
G509L
-
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
H539S
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active site mutant
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
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
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
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/Q151M/A62V/V75I/F77L/F116Y
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
L100I
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
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
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
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
Q500A
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mutation reduces the viral titer less than 2-fold
R557A
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the mutant shows about 5fold reduced kcat value compared to the wild type enzyme
R557S
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active site mutant
T369I
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mutation in the connection domain
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
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
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
W88G
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mutation involved in foscarnet resistance
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
Y318F
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mutation in the connection domain
E478Q
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RNase H active site mutant
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E478Q/N348I
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mutation of RNase H active site and connection domain
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K103N
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a classic NNRTI resistance mutation
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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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Y181C
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a classic NNRTI resistance mutation
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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
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+
D653N
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4% of wild-type activity
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
H638G
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15% of wild-type activity
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
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 hide
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