Literature summary for 3.1.13.2 extracted from

Schultz, S.J.; Champoux, J.J.
RNase H activity: structure, specificity, and function in reverse transcription (2008), Virus Res., 134, 86-103.

Search for more literature for 3.1.13.2

Application

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 (Commentary)

Crystallization (Comment)	Organism
-	Moloney murine leukemia virus
-	Human immunodeficiency virus 1

Protein Variants

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

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

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 [Da]	Molecular Weight Maximum [Da]	Comment	Organism
76000	-	-	Moloney murine leukemia virus

Natural Substrates/ Products (Substrates)

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

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

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	a
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	a

Substrates and Products (Substrate)

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

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

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

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)