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Literature summary for 3.1.13.2 extracted from

  • Sarafianos, S.G.; Marchand, B.; Das, K.; Himmel, D.M.; Parniak, M.A.; Hughes, S.H.; Arnold, E.
    Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition (2009), J. Mol. Biol., 385, 693-713.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.13.2

Application

Application Comment Organism
drug development viruses deficient in RNase H activity are non-infectious making RNase H an interesting target for anti-HIV inhibitors Human immunodeficiency virus 1

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structures of full-length HIV-1 reverse transcriptase with a DNA/DNA or RNA/DNA substrate show a distance of about 60 A between the polymerase active site and the RNase H active site Human immunodeficiency virus 1

Inhibitors

Inhibitors Comment Organism Structure
2'-deoxy-4'-ethyl-3,4-dihydrothymidine
-
 Human immunodeficiency virus 1
2'-deoxy-4'-ethynyl-2-fluoroadenosine
-
 Human immunodeficiency virus 1
2'-deoxy-4'-methyl-3,4-dihydrothymidine
-
 Human immunodeficiency virus 1
2,7-dihydroxy-4-isopropylcyclohepta-2,4,6-trienone 2,7-dihydroxy-4-1(methylethyl)-2,4,6-cycloheptatrien-1-one, or beta-thujaplicinol, is not candidate therapeutics because it is cytotoxic Human immunodeficiency virus 1
3,4-dihydroxy-N'-[(E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide specific inhibitor of reverse transcriptase RNase H activity (IC50 value is about 0.5 microM) and has relatively limited activity against the DNA polymerase activity of reverse transcriptase. It is non-cytotoxic and inhibits the replication of a variety of drug-resistant HIV-1 reverse transcriptase mutants Human immunodeficiency virus 1
4-[5-benzoylamino) thien-2-yl]-2,4-dioxobutanoic acid inhibits RNase H by binding to the active site and chelating the essential Mg2+ Human immunodeficiency virus 1
5-chloro-2-hydroxyisoquinoline-1,3(2H,4H-dione) is not candidate therapeutics because it is cytotoxic Human immunodeficiency virus 1
BPH218 potent inhibitor of ATP-mediated phosphorolytic excision of 3'-terminal zidovudine 5'-monophosphate (in vitro IC50 value is about 2 microM) Human immunodeficiency virus 1
N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone reasonable potency. Bifunctional inhibitor of HIV-1 reverse transcriptase, it inhibits both the reverse transcriptase DNA polymerase and RNase H activities of the enzyme with similar potency (IC50 is about 3 microM) Human immunodeficiency virus 1
[(4-chlorophenyl) hydrazono] propanedioic acid inhibits the RNase H of HIV-1 reverse transcriptase with potency similar to that of N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone. It is specific for RNase H and does not inhibit the DNA polymerase activity of reverse transcriptase. Inhibits RNase H by binding to the active site and chelating the essential Mg2+ Human immunodeficiency virus 1

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ optimal RNase H activity is obtained in the presence of one Mg2+ and one Mn2+ Human immunodeficiency virus 1
Mn2+ optimal RNase H activity is obtained in the presence of one Mg2+ and one Mn2+ Human immunodeficiency virus 1

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Human immunodeficiency virus 1 cleaves RNA only if the RNA is part of an RNA/DNA duplex ?
-
 ?

Organism

Organism UniProt Comment Textmining
Human immunodeficiency virus 1
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
DNA-RNA hybrid + H2O RNase H cleaves precisely one nucleotide from the tRNA/DNA junction, leaving a ribo-A on the 3' end of the viral minus-strand DNA Human immunodeficiency virus 1 ?
-
 ?
additional information cleaves RNA only if the RNA is part of an RNA/DNA duplex Human immunodeficiency virus 1 ?
-
 ?
additional information both of the enzymatic functions of reverse transcriptase, the DNA polymerase and RNase H, are essential for copying the single-stranded RNA genome found in virions into the double-stranded DNA that is inserted into the host genome by IN Human immunodeficiency virus 1 ?
-
 ?

Subunits

Subunits Comment Organism
More reverse transcriptase is a heterodimer. The larger subunit, p66, contains the active sites for both of the enzymatic activities of reverse transcriptase (polymerase and RNase H), the smaller subunit has a structural role Human immunodeficiency virus 1

Synonyms

Synonyms Comment Organism
RNase H reverse transcriptase domain Human immunodeficiency virus 1

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0005
-
 IC50 value is about 0.5 microM Human immunodeficiency virus 1 3,4-dihydroxy-N'-[(E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide
0.002
-
 in vitro IC50 value is about 2 microM Human immunodeficiency virus 1 BPH218
0.003
-
 IC50 is about 3 microM Human immunodeficiency virus 1 N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone