3.1.26.13: retroviral ribonuclease H
This is an abbreviated version!
For detailed information about retroviral ribonuclease H, go to the full flat file.
Word Map on EC 3.1.26.13
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3.1.26.13
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integrase
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hiv-rt
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rna-dna
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template-primer
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moloney
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polypurine
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transcriptases
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minus-strand
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3'-azido-3'-deoxythymidine
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nnrti
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primer-template
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nonnucleoside
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drug development
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medicine
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analysis
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pharmacology
- 3.1.26.13
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integrase
- hiv-rt
- rna-dna
-
template-primer
-
moloney
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polypurine
- transcriptases
-
minus-strand
- 3'-azido-3'-deoxythymidine
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nnrti
-
primer-template
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nonnucleoside
- drug development
- medicine
- analysis
- pharmacology
Reaction
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. =
Synonyms
HIV reverse transcriptase ribonuclease H, HIV reverse transcriptase-associated RNase H, HIV RNase H, HIV RT RNaseH, HIV RT-associated RNase H, HIV-1 reverse transcriptase, HIV-1 reverse transcriptase ribonuclease H, HIV-1 reverse transcriptase RNase H, HIV-1 RH, HIV-1 ribonuclease H, HIV-1 ribonuclease H domain, HIV-1 RNase H, HIV-1 RT-associated RNase H, human immunodeficiency virus reverse transcriptase, human immunodeficiency virus reverse transcriptase-associated ribonuclease H, human immunodeficiency virus reverse transcriptase-associated RNase H, human immunodeficiency virus RT-associated RNase H, M-MuLV RT RNase H, reverse transcriptase, reverse transcriptase-associated ribonuclease H, reverse transcriptase-associated RNase H, reverse-transcriptase-associated ribonuclease H, ribonuclease H, ribonuclease H domain in HIV-1 reverse transcriptase, RNase H, RNase H activity of HIV-1 reverse transcriptase, RNase H domain of HIV-1 reverse transcriptase, RNase H of HIV-1 subtype C, RNaseH, RNH, RNHHIV, RT RNase H, RT-RNase H
ECTree
3.1.26.13 retroviral ribonuclease HAdvanced search results
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Engineering on EC 3.1.26.13 - retroviral ribonuclease H
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D549A
-
mutation in polypeptide p66, decrease in RNase H activity
D549N
-
mutation in polypeptide p66, decrease in RNase H activity
E478Q
Q294P
-
site-directed mutagenesis, the Q294P mutant of HIV-2 RT has about 10fold higher RNase H activity than the wild-type. Infectious HIV-2 cannot bear the replacement of the RT's Gln294 by the HIV-1 RT Pro counterpart, as it results in substantially reduced HIV-2 replication and fast reversions to the wild-type Gln294 virus
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
A360V
A371V
A376S
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
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
C280S
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
C282S
-
site-directed mutagenesis, the mutation avoids non-specific cross-linking in both subunits, p66 and p51 subunits of HIV-1
D443A
-
site-directed mutagenesis, altered inhibitor binding compared to wild-type enzyme
D549A
-
site-directed mutagenesis, altered inhibitor binding compared to wild-type enzyme
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
E312Q
E396A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
E438N
site-directed mutagenesis, the mutation disrupts RNH folding, viral infectivity is eliminated by the mutation
E438N/T477A
site-directed mutagenesis, addition of the T477A mutation restores correct folding of the RNH domain despite the presence of the E438N mutation
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
E478A
-
site-directed mutagenesis, altered inhibitor binding compared to wild-type enzyme
E478Q
E478Q/N348I
-
mutation of RNase H active site and connection domain
E706Q
F227L
-
mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
F440A
site-directed mutagenesis, the mutation disrupts RNH folding, viral infectivity is eliminated by the mutation. Molecular dynamics simulations suggest that the T477A mutation affects the processing site by altering relative orientations of secondary structure elements
F440A/T477A
site-directed mutagenesis, addition of the T477A mutation restores correct folding of the RNH domain despite the presence of the F440A mutation
G190A
G190S
-
site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
G333E
G335C
-
mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
G335D
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
-
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
-
mutation in isolated RNase H domain, mutant fails to bind RNA/DNA hybrids. Structure of mutant is similar to wild-type
H539N
-
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
-
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
-
thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
K219N
-
thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
K219Q
K390A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K395A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
K451R
-
mutation present in viral isolates of 11% of antiviral treatment-experienced patients but remaining 100% conserved among treatment-naive patients
K476A
K540A
-
site-directed mutagenesis, altered inhibitor binding compared to wild-type enzyme
K558E
-
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
-
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
-
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
-
mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
K70R
L100I
-
mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
L210W
L429M/E514L
N-terminal truncated constructs include RHDELTANT, corresponding to p66 residues 429-560 with an N-terminal Leu429Met mutation, an extended linker construct, RHDELTANT-EL, in which an additional Pro-Asp-Gln sequence is introduced into RHDELTANT immediately following Gln512, and RHDELTANT(E514L) in which RHDELTANT contains an E514L substitution in the alphaB-alphaD linker
L469H
-
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
-
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
-
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
-
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
-
mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
M184V
-
naturally occuring mutation in HIV infection patients, arises with abacavir, emtricitabine, or lamivudine treatment
M230L
-
the naturally occuring mutation leads to reduced RNase H activity of the HIV reverse transcriptase
M41L
N348I
N474A
N474A/Q475A
-
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
-
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
-
site-directed mutagenesis, the mutant virus shows substantially reduced fitness compared to that of the wild-type virus
P537Stop
-
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
-
mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
Q151M/A62V/V75I/F77L/F116Y
-
mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
Q475A
Q475E
-
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
-
the mutant shows about 5fold reduced kcat value compared to the wild type enzyme
R72A
-
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type. The R72A mutation might impair the nucleotide-induced conformational change but does not affect the RNase H activity directly, kinetic parameters governing TTP binding and incorporation by the HIVRT mutant, overview. The mutation causes impaired TTP induced conformational change on RNase H activity
T215F
T215Y
T470E
-
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
-
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
-
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
-
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
-
the mutation increases the sensitivity of the enzyme for inhibitor NSC727447 by 50fold
T473M
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
T477A
site-directed mutagenesis, addition of the T477A mutation restores correct folding of the RNH domain despite the presence of the F440A or E438N mutations
V106A
V365I
V552Stop
-
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
-
mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
W229F/Y232W
-
mutation in primer grip residues, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
W229Y
-
mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
W535A
-
site-directed mutagenesis, altered inhibitor binding compared to wild-type enzyme
W71A
-
site-directed mutagenesis, the mutant is probably less rigidly locked on the substrate DNA/RNA hybrid, parameters governing TTP binding and incorporation by the HIVRT mutant, overview. The mutation causes impaired TTP induced conformational change on RNase H activity
W71D
-
site-directed mutagenesis, the mutant is probably less rigidly locked on the substrate DNA/RNA hybrid, parameters governing TTP binding and incorporation by the HIVRT mutant, overview. The mutation causes impaired TTP induced conformational change on RNase H activity
Y181C
Y188C
-
mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
Y188L
-
mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
Y229F/Y232F
-
mutation in primer grip residues, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
Y232W
-
mutation in primer grip residue, specificity of cleavage is not compromised, efficiency is reduced to 33-44% of wild-type
Y501A
E478Q/N348I
-
mutation of RNase H active site and connection domain
-
N348I
-
connection domain mutant, altered RNase H cleavage pattern compared to the wild-type HIV-1 RT
-
E396A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
-
K390A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
-
K395A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
-
K65R
-
naturally occuring mutation in HIV infection patients, arises with abacavir, didanosine, emtricitabine, lamivudine, or tenofovir disoproxil fumarate treatment
-
M230L
-
the naturally occuring mutation leads to reduced RNase H activity of the HIV reverse transcriptase
-
Y501A
-
naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
-
Q294P
-
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
D443N
Human immunodeficiency virus type 1 group M subtype B
RNase H inactivating mutation, the mutant is devoid of strand transfer activity
E478Q
Human immunodeficiency virus type 1 group M subtype B
RNase H inactivating mutation, the mutant is devoid of strand transfer activity
G140S/Q148H
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant INSTI
K70R
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NRTI
L100I/K103N
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NNRTI
M184V
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NRTI
V106A
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NNRTI
Y181C
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NNRTI
Y188L
Human immunodeficiency virus type 1 group M subtype B
site-directed mutagenesis, mutant NNRTI
D443N
Human immunodeficiency virus type 1 group M subtype B BH10
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RNase H inactivating mutation, the mutant is devoid of strand transfer activity
-
E478Q
Human immunodeficiency virus type 1 group M subtype B BH10
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RNase H inactivating mutation, the mutant is devoid of strand transfer activity
-
K70R
Human immunodeficiency virus type 1 group M subtype B BH10
-
site-directed mutagenesis, mutant NRTI
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M184V
Human immunodeficiency virus type 1 group M subtype B BH10
-
site-directed mutagenesis, mutant NRTI
-
V106A
Human immunodeficiency virus type 1 group M subtype B BH10
-
site-directed mutagenesis, mutant NNRTI
-
Y181C
Human immunodeficiency virus type 1 group M subtype B BH10
-
site-directed mutagenesis, mutant NNRTI
-
Y188L
Human immunodeficiency virus type 1 group M subtype B BH10
-
site-directed mutagenesis, mutant NNRTI
-
D443N
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
E478Q
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
F61A
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
K358R/A359G/S360A
Human immunodeficiency virus type 1 group O subtype B
-
the mutant shows highly increased strand transfer efficiency compared to wild-type
K65R/E478Q
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
L92P
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
L92P/D443N
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows decreased dissociation rate constant (koff) compared to wild-type
L92P/E478Q
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
T355A/Q357M
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
T355A/Q357MK358R/A359G/S360A
Human immunodeficiency virus type 1 group O subtype B
-
the mutant shows highly increased strand transfer efficiency compared to wild-type
V148I
Human immunodeficiency virus type 1 group O subtype B
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
V148I/K358R/A359G/S360A
Human immunodeficiency virus type 1 group O subtype B
-
the mutant shows highly increased strand transfer efficiency compared to wild-type
D443N
Human immunodeficiency virus type 1 group O subtype B ESP49
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
-
E478Q
Human immunodeficiency virus type 1 group O subtype B ESP49
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
-
L92P
Human immunodeficiency virus type 1 group O subtype B ESP49
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
-
V148I
Human immunodeficiency virus type 1 group O subtype B ESP49
-
site-directed mutagenesis, the mutant shows increased dissociation rate constant (koff) compared to wild-type
-
A554S
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
D460N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
D488E
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
D549N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
E529D
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
H539N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
I505A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
I506L
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K451R
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K476A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K476N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K512Q
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K527N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K530R
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K558E
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
K558R
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
L469F
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
L491S
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
N474A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Q475A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Q500A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Q509L
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Q547K
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
T470N
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
T473A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
V518I
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Y501A
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
Y501F
Human immunodeficiency virus type 1 subtype C
-
naturally occurring mutation in the RNase H region of HIV-1 subtype C infected individual
A128T
-
the mutant strain is resistant to 2-hydroxyisoquinoline-1,3(2H,4H)-dione inhibitors in contrast to the wild-type
C635V
-
site-directed mutagenesis, the mutant shows slightly reduced reverse transcriptase and RNAse H activities compared the wild-type enzyme
D524A
D524N
D583A
-
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
-
less than 0.5% of wild-type activity, no binding of Mn2+
E562Q
-
less than 0.5% of wild-type activity, no binding of Mn2+
G140S/Q148H
-
the mutant strain is resistant to 2-hydroxyisoquinoline-1,3(2H,4H)-dione inhibitors in contrast to the wild-type
D358N
-
mutation eliminates Mg2+- and Mn2+-dependent RNase H function
D426N
-
mutation eliminates Mg2+- and Mn2+-dependent RNase H function
D469N
-
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
-
mutation eliminates Mg2+- and Mn2+-dependent RNase H function
H427A
-
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
-
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
-
the efficiency with which mutant RT catalyzes transfer of nascent DNA between RNA templates is severely reduced
A360V
-
mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
A360V
-
naturally occuring mutant from clinical isolates, a connection/RNase H domain mutant that shows reduced RNase H activity
A371V
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
-
site-directed mutagenesis, a connection/RNase H domain mutant
A376S
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
-
mutation in the connection domain, the mutation significantly contributes to zidovudine resistance
D67N
-
thymidine analogue mutation, TAMs, arising with zidovudine and stavudine treatment, take the TAM-2 pathway
E312Q
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
E706Q
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site-directed mutagenesis of HIV-1 reverse transcriptase, inactive mutant
E706Q
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site-directed mutagenesis of the recombinant mutant construct G, E706 in construct G corresponds to E478 in HIV-1 reverse transcriptase, inactive mutant
G190A
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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
G190A
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site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
G333E
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
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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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
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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site-directed mutagenesis, the mutation does not affect RNase H function
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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naturally occuring mutation in HIV infection patients, the mutation increases zidovudine resistance and decreased reverse trancriptase template switching
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
K65R
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mutation involved in nucleos(t)ide reverse transcriptase inhibitor resistance
K65R
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naturally occuring mutation in HIV infection patients, arises with abacavir, didanosine, emtricitabine, lamivudine, or tenofovir disoproxil fumarate treatment
K70R
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naturally occuring mutation in HIV infection patients, is common to stavudine, tenofovir disoproxil fumarate, and zidovudine therapy
K70R
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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
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
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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mutation involved in non-nucleoside reverse transcriptase inhibitor resistance
V106A
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site-directed mutagenesis, the mutant virus shows moderately reduced fitness compared to that of the wild-type virus
V365I
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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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
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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site-directed mutagenesis, the mutation does not affect RNase H function
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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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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the mutant shows about 400fold reduced kcat valuecompared to 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
D524A
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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
D524N
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less than 0.5% of wild-type activity, no binding of Mn2+
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
additional information
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an HIV-1 mutant can tolerate an about 10fold higher RNase H activity
additional information
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naturally occurring polymophisms at position 294 in HIV-2 are Q, E, L, H, and K
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 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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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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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
effect of N-terminal deletion on monomer-dimer interconversion kinetics, overview. The mutant exhibits large perturbations of the Ile522 and Ile526 resonances corresponding to residues located near the Tyr427 binding pocket, as well as smaller but significant perturbations for several other Ile resonances, consistent with a more subtle, global structural perturbation. As a result of the faster monomer-dimer interconversion rate, even the initial spectrum obtained for the purified dimer sample exhibits significant monomer resonances
additional information
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effect of N-terminal deletion on monomer-dimer interconversion kinetics, overview. The mutant exhibits large perturbations of the Ile522 and Ile526 resonances corresponding to residues located near the Tyr427 binding pocket, as well as smaller but significant perturbations for several other Ile resonances, consistent with a more subtle, global structural perturbation. As a result of the faster monomer-dimer interconversion rate, even the initial spectrum obtained for the purified dimer sample exhibits significant monomer resonances
additional information
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mutation of the N-terminal residue of RNase H which is important in the life cycle of HIV-1, change of this residue to several different amino acids. Selection of mutants is based on the N-end rule designation or the structure of the specific amino acid compared to that of the wild-type residue of tyrosine. Compared to wild-type AETF/YVD, the mutants show the following cleavage sites: AETF/MVD, AETF/FVD, AETF/WVD, AETF/TVD, AETF/LVD, AETF/KVD, AETF/AVD, AETF/PVD, AETF/GVD, AETF/SVD, and AETF/VVD, being stabilizing or destabilizing for the N-end rule, packaging and processing of viral polyproteins with RNaseH N-terminal mutations, overview. Reverse transcriptase with an RNase H N-terminal mutation is still degraded in the absence of active viral protease
additional information
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the isolated RNase H domain of HIV-1 RT (RNHHIV) is inactive, possibly due to the lack of a substrate binding ability, disorder of a loop containing His539, and increased flexibility. To examine whether the activity of RNHHIV is restored by the attachment of TmaHBD or BstNTD to its N-terminus, two chimeric proteins, TmaHBD-RNHHIV and BstNTD-RNHHIV, are constructed and characterized. Both chimeric proteins bind to RNA/DNA hybrid more strongly than RNHHIV and exhibit enzymatic activity in the presence of Mn2+ ions. They do not exhibit activity or exhibited very weak activity in the presence of Mg2+ ions
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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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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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
Human immunodeficiency virus type 1 group O subtype B
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the kinetics of wild-type and mutant enzymes are determined with the RNA/DNA template-primer R33B/20A. Rates of nontemplated nucleotide addition of wild-type and mutant HIV-1 RTs using blunt-ended DNA/DNA substrates, overview. Non-templated nucleotide addition and strand transfer are mechanistically independent
additional information
Human immunodeficiency virus type 1 group O subtype B ESP49
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the kinetics of wild-type and mutant enzymes are determined with the RNA/DNA template-primer R33B/20A. Rates of nontemplated nucleotide addition of wild-type and mutant HIV-1 RTs using blunt-ended DNA/DNA substrates, overview. Non-templated nucleotide addition and strand transfer are mechanistically independent
-
additional information
Human immunodeficiency virus type 1 subtype C
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characterization of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations in the RNase H region of HIV-1 subtype C infected individuals, overview. Mutations are identified by comparing with NRTI-associated RNase H mutations previously identified from subtype B drug-resistance studies
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
