Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for anti-HIV drug development | Human immunodeficiency virus 1 |
Crystallization (Comment) | Organism |
---|---|
enzyme bound to inhibitor (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide, by vapor diffusion in microseeded hanging drops containing equal volumes of protein and reservoir solution containing 50 mM imidazole, pH 6.4, 100 mM ammonium sulfate, 15 mM magnesium sulfate, 5% glucose, 11.5% PEG 8000 at 4°C, mixing 0.0074 ml of 20 mM inhibitor in DMSO with 0.0025 ml of 20% beta-octyl glucopyranoside, of this solution, 0.0075 ml is combined with 0.065 ml of 40 mg/ml RT and 0.0575 ml of additional RT buffer containing 10 mM Tris, pH 8.0, and 75 mM NaCl on ice, X-ray diffraction structure determination and anaylsis at 3.15 A resolution | Human immunodeficiency virus 1 |
Protein Variants | Comment | Organism |
---|---|---|
D67N/K70R/T215F/K219Q | the mutant shows reduced sensitivity to inhibitor (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | Human immunodeficiency virus 1 |
V106A/Y181C | the mutant shows reduced sensitivity to inhibitor (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | Human immunodeficiency virus 1 |
Y181C | the mutant shows reduced sensitivity to inhibitor (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | Human immunodeficiency virus 1 |
Y188L | the mutant shows reduced sensitivity to inhibitor (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | Human immunodeficiency virus 1 |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | i.e. DHBNH, highly specific, noncompetitive, binding site analysis, the inhibitor binds near both the polymerase active site and the non-nucleoside reverse transcriptase inhibitor binding pocket, it specifically interacts with conserved residues Asp186 and Trp229 and has substantial interactions with the backbones of several less well-conserved residues, overview, substituted inhibitor derivatives, that interact with the nucleoside analog RT inhibitor-binding pocket, inhibit both the polymerase and RNH activities of reverse transcriptase, DHBNH interacts with other residues, including Val108, Leu187, Tyr188, Lys223, Phe227, and Leu228 | Human immunodeficiency virus 1 | |
4'-chloro-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]biphenyl-4-carbohydrazide | - |
Human immunodeficiency virus 1 | |
4-(dimethylamino)-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | - |
Human immunodeficiency virus 1 | |
4-methoxy-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | - |
Human immunodeficiency virus 1 | |
4-tert-butyl-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | - |
Human immunodeficiency virus 1 | |
additional information | inhibition mechanism, overview, antiviral activity and cytotoxic effects of inhibitors, overview | Human immunodeficiency virus 1 | |
N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]-4-methylbenzohydrazide | - |
Human immunodeficiency virus 1 | |
N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]-4-phenoxybenzohydrazide | - |
Human immunodeficiency virus 1 | |
N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | - |
Human immunodeficiency virus 1 | |
N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]biphenyl-4-carbohydrazide | - |
Human immunodeficiency virus 1 | |
N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone | i.e. BBNH, highly specific, a substituted inhibitor derivative, that interacts with the nucleoside analog RT inhibitor-binding pocket, and inhibits both the polymerase and RNH activities of reverse transcriptase | Human immunodeficiency virus 1 | |
N-acyl hydrazone analogues | - |
Human immunodeficiency virus 1 |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
K+ | - |
Human immunodeficiency virus 1 | |
Mg2+ | - |
Human immunodeficiency virus 1 |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
DNA-RNA hybrid + H2O | Human immunodeficiency virus 1 | - |
DNA + RNA nucleotides | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Human immunodeficiency virus 1 | P03366 | i.e. HIV-1 | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
DNA-RNA hybrid + H2O | - |
Human immunodeficiency virus 1 | DNA + RNA nucleotides | - |
? | |
DNA-RNA hybrid + H2O | - |
Human immunodeficiency virus 1 | DNA nucleotides + RNA nucleotides | - |
? | |
additional information | the reverse transcriptase has two enzyme activities, one of which is the RNase H, enzyme-ligand interactions, overview | Human immunodeficiency virus 1 | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | HIV-1 reverse transcriptase is a heterodimer consisting of a 66 kDa p66 subunit and a 51 kDa p51 subunit. The two polypeptide chains have 440 N-terminal amino acid residues in common, these comprise four polymerase subdomains: the thumb, palm, fingers, and connection, the C-terminus of p66 contains an additional 120 amino acid residues that form the bulk of the RNH domain | Human immunodeficiency virus 1 |
Synonyms | Comment | Organism |
---|---|---|
RNase H | - |
Human immunodeficiency virus 1 |
RNH | - |
Human immunodeficiency virus 1 |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Human immunodeficiency virus 1 |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Human immunodeficiency virus 1 |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
additional information | - |
inhibition of mutant enzymes by DHBNH and antiviral activity, overview | Human immunodeficiency virus 1 | additional information | |
0.0005 | - |
- |
Human immunodeficiency virus 1 | (E)-3,4-dihydroxy-N'-((2-methoxynaphthalen-1-yl)methylene)benzohydrazide | |
0.002 | - |
- |
Human immunodeficiency virus 1 | 4-(dimethylamino)-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | |
0.003 | - |
- |
Human immunodeficiency virus 1 | 4-tert-butyl-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | |
0.005 | - |
- |
Human immunodeficiency virus 1 | N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]biphenyl-4-carbohydrazide | |
0.007 | - |
- |
Human immunodeficiency virus 1 | N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]-4-phenoxybenzohydrazide | |
0.0075 | - |
- |
Human immunodeficiency virus 1 | 4'-chloro-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]biphenyl-4-carbohydrazide | |
0.012 | - |
- |
Human immunodeficiency virus 1 | 4-methoxy-N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | |
0.015 | - |
- |
Human immunodeficiency virus 1 | N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]benzohydrazide | |
0.015 | - |
- |
Human immunodeficiency virus 1 | N'-[(1E)-(2-methoxynaphthalen-1-yl)methylidene]-4-methylbenzohydrazide |