Application | Comment | Organism |
---|---|---|
drug development | RNase H is an anti-viral target | Moloney murine leukemia virus |
drug development | RNase H is an anti-viral target | Human immunodeficiency virus 1 |
drug development | reverse transcriptase is a primary target for antiretroviral therapy of HIV-1 infected patients. While the vast majority of anti-virals are specific for the polymerase domain, the RNaseH activity of reverse transcriptase represents an excellent target for antiretroviral drugs as well | Moloney murine leukemia virus |
drug development | reverse transcriptase is a primary target for antiretroviral therapy of HIV-1 infected patients. While the vast majority of anti-virals are specific for the polymerase domain, the RNaseH activity of reverse transcriptase represents an excellent target for antiretroviral drugs as well | Human immunodeficiency virus 1 |
Crystallization (Comment) | Organism |
---|---|
- |
Moloney murine leukemia virus |
- |
Human immunodeficiency virus 1 |
Protein Variants | Comment | Organism |
---|---|---|
K103N | naturally occuring mutations leading to reduced RNase H activity and increased resistance of the reverse trancriptase to NRTIs | Human immunodeficiency virus 1 |
additional information | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, NRTIs, e.g. 3'-azido-3'-deoxythymidine, mutations in the RNase H domain that decrease RNase H activity can increase the resistance of reverse transcriptase to NRTIs, overview | Moloney murine leukemia virus |
additional information | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, NRTIs, e.g. 3'-azido-3'-deoxythymidine, mutations in the RNase H domain that decrease RNase H activity can increase the resistance of reverse transcriptase to NRTIs, overview | Human immunodeficiency virus 1 |
P236L | naturally occuring mutations leading to reduced RNase H activity and increased resistance of the reverse trancriptase to NRTIs | Human immunodeficiency virus 1 |
V106A | naturally occuring mutations leading to reduced RNase H activity and increased resistance of the reverse trancriptase to NRTIs | Human immunodeficiency virus 1 |
Y181C | naturally occuring mutations leading to reduced RNase H activity and increased resistance of the reverse trancriptase to NRTIs | Human immunodeficiency virus 1 |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
3'-azido-3'-deoxythymidine | a nucleoside analog RT inhibitor | Human immunodeficiency virus 1 | |
3'-azido-3'-deoxythymidine | a nucleoside analog RT inhibitor | Moloney murine leukemia virus | |
additional information | one potential class of RNase H inhibitors involves drugs that alter the interactions between the RNase H domain and substrate or that alter the alignment of substrate in the RNase H active site | Human immunodeficiency virus 1 | |
additional information | one potential class of RNase H inhibitors involves drugs that alter the interactions between the RNase H domain and substrate or that alter the alignment of substrate in the RNase H active site | Moloney murine leukemia virus | |
non-nucleoside reverse transcriptase inhibitors | i.e. NNRTIs, the association of an NNRTI with reverse transcriptase not only forms the NNRTI pocket, but also alters the relative positions of the RNase H and polymerase domains | Human immunodeficiency virus 1 | |
non-nucleoside reverse transcriptase inhibitors | i.e. NNRTIs | Moloney murine leukemia virus | |
non-nucleotide or non-nucleoside reverse transcriptase inhibitor | NNRTI, non-competitive inhibitor that binds a hydrophobic pocket near the polymerase active site of the p66 subunit in HIV-1 reverse transcriptase | Human immunodeficiency virus 1 | |
non-nucleotide or non-nucleoside reverse transcriptase inhibitor | targets the DNA polymerasec activity of reverse transcriptase. Non-competitive inhibitor that binds a hydrophobic pocket near the polymerase active site of the p66 subunit in HIV-1 reverse transcriptase | Moloney murine leukemia virus | |
nucleoside analog RT inhibitors | i.e. NRTIs, nucleoside analog RT inhibitors are non-competitive inhibitors that bind a hydrophobic pocket near the polymerase active site of the p66 subunit in HIV-1 reverse transcriptase | Human immunodeficiency virus 1 | |
nucleoside analog RT inhibitors | i.e. NRTIs, nucleoside analog RT inhibitors are non-competitive inhibitors | Moloney murine leukemia virus | |
nucleotide or nucleoside reverse transcriptase inhibitor | NRTIs inhibit replication by competing with cellular dNTPs for incorporation into the nascent DNAchain; upon incorporation, the absence of a 3' hydroxyl group on the NRTI prevents additional synthesis and causes premature chain termination | Human immunodeficiency virus 1 | |
nucleotide or nucleoside reverse transcriptase inhibitor | targets the DNA polymerasec activity of reverse transcriptase. NRTIs inhibit replication by competing with cellular dNTPs for incorporation into the nascent DNAchain; upon incorporation, the absence of a 3' hydroxyl group on the NRTI prevents additional synthesis and causes premature chain termination | Moloney murine leukemia virus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Moloney murine leukemia virus | |
Mg2+ | a single ion is bound at the RNase H active site | Human immunodeficiency virus 1 |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
76000 | - |
- |
Moloney murine leukemia virus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Moloney murine leukemia virus | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, i.e. NRTIs | ? | - |
? | |
additional information | Human immunodeficiency virus 1 | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, i.e. NRTIs | ? | - |
? | |
additional information | Moloney murine leukemia virus | retroviral RNases H display three different modes of cleavage: internal, DNA 3' end-directed, and RNA 5' end-directed | ? | - |
? | |
additional information | Human immunodeficiency virus 1 | retroviral RNases H display three different modes of cleavage: internal, DNA 3' end-directed, and RNA 5' end-directed | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Human immunodeficiency virus 1 | P03366 | - |
- |
Human immunodeficiency virus 1 | P03366 | i.e. HIV-1 | - |
Moloney murine leukemia virus | - |
i.e. MoMLV | - |
Moloney murine leukemia virus | P03355 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid | RNase H utilizes a two-metal ion mechanism of catalysis, the first metal ion A activates the nucleophilic water molecule and the second metal ion B, possibly in conjunction with metal ion A, stabilizes the transition state intermediate, catalytic residues are Asp443, Glu478, Asp498 and Asp549, substrate interactions, reaction mechanism and cleavage mode, overview | Human immunodeficiency virus 1 | |
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid | RNase H utilizes a two-metal ion mechanism of catalysis, the first metal ion A activates the nucleophilic water molecule and the second metal ion B, possibly in conjunction with metal ion A, stabilizes the transition state intermediate, substrate interactions, reaction mechanism and cleavage mode, overview | Moloney murine leukemia virus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
DNA-RNA hybrid + H2O | - |
Moloney murine leukemia virus | ? | - |
? | |
DNA-RNA hybrid + H2O | - |
Human immunodeficiency virus 1 | ? | - |
? | |
DNA/DNA + H2O | RNase H catalysis by the retroviral enzyme appears to involve a two-metal ion mechanism. Unlike cellular RNases H, the retroviral RNase H displays three different modes of cleavage: internal, 3'-end-DNA-directed, and 5'-end-RNA-directed, all three modes of cleavage appear to have essential roles in reverse transcription, overview, cleavage site selection modelling, RNase H activities of human retroviral reverse transcriptases preferentially cleave between two ribonucleotide residues in an RNA chain, and between the penultimate and last ribonucleotide of an extended RNA primer rather than precisely at the RNA-DNA junction, overview | Human immunodeficiency virus 1 | ? | - |
? | |
DNA/DNA + H2O | RNase H catalysis by the retroviral enzyme appears to involve a two-metal ion mechanism. Unlike cellular RNases H, the retroviral RNase H displays three different modes of cleavage: internal, 3'-end-DNA-directed, and 5'-end-RNA-directed, all three modes of cleavage appear to have essential roles in reverse transcription, overview, RNase H activities of murine retroviral reverse transcriptases preferentially cleave between two ribonucleotide residues in an RNA chain, and between the penultimate and last ribonucleotide of an extended RNA primer rather than precisely at the RNA-DNA junction | Moloney murine leukemia virus | ? | - |
? | |
additional information | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, i.e. NRTIs | Moloney murine leukemia virus | ? | - |
? | |
additional information | mutations in reverse transcriptase outside of the polymerase domain may have clinical significance in resistance to nucleoside analog RT inhibitors, i.e. NRTIs | Human immunodeficiency virus 1 | ? | - |
? | |
additional information | the polymerization-dependent RNase H activity is insufficient to completely degrade the genomic template during minus-strand synthesis, pausing by reverse transcriptase during transcription promotes RNase H cleavages and facilitates strand transfers, overview, cleavage site selection modelling, overview, the isolated MoMLV RNase H domain retains enzymatic activity, but is unable to carry out specific cleavages such as removal of the tRNA or PPT primers in vitro, cleavage specificity of RNase H, overview | Moloney murine leukemia virus | ? | - |
? | |
additional information | the polymerization-dependent RNase H activity is insufficient to completely degrade the genomic template during minus-strand synthesis, pausing by reverse transcriptase during transcription promotes RNase H cleavages and facilitates strand transfers, the isolated RNase H domain of HIV-1 is inactive, but nuclease activity is reconstituted by introducing the p51 subunit, by adding the thumb and connection subdomains, or by various N-terminal fusions on the RNase H domain, cleavage specificity of RNase H, overview | Human immunodeficiency virus 1 | ? | - |
? | |
additional information | retroviral RNases H display three different modes of cleavage: internal, DNA 3' end-directed, and RNA 5' end-directed | Moloney murine leukemia virus | ? | - |
? | |
additional information | retroviral RNases H display three different modes of cleavage: internal, DNA 3' end-directed, and RNA 5' end-directed | Human immunodeficiency virus 1 | ? | - |
? | |
RNA/DNA hybrid + H2O | i.e. 18 nucleotide 3'-fluorescein-labeled RNA annealed to a complementary 18 nucleotide 5'-dabsyl-modified DNA, RNase H catalysis by the retroviral enzyme appears to involve a two-metal ion mechanism. Unlike cellular RNases H, the retroviral RNase H displays three different modes of cleavage: internal, 3'-end-DNA-directed, and 5'-end-RNA-directed, all three modes of cleavage appear to have essential roles in reverse transcription, overview, substrate binding structure, overview | Human immunodeficiency virus 1 | ? | - |
? | |
RNA/DNA hybrid + H2O | RNase H catalysis by the retroviral enzyme appears to involve a two-metal ion mechanism. Unlike cellular RNases H, the retroviral RNase H displays three different modes of cleavage: internal,3'-end-DNA-directed, and 5'-end-RNA-directed, all three modes of cleavage appear to have essential roles in reverse transcription, overview | Moloney murine leukemia virus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterodimer | - |
Human immunodeficiency virus 1 |
monomer | - |
Moloney murine leukemia virus |
More | viral RNase H domain structure including the RNase H primer grip and C-helix and loop structures, connection subdomain, overview | Human immunodeficiency virus 1 |
More | viral RNase H domain structure, overview | Moloney murine leukemia virus |
Synonyms | Comment | Organism |
---|---|---|
RNase H | - |
Moloney murine leukemia virus |
RNase H | - |
Human immunodeficiency virus 1 |
RNase H | domain of reverse transcriptase | Moloney murine leukemia virus |
RNase H | domain of reverse transcriptase | Human immunodeficiency virus 1 |