Cloned (Comment) | Organism |
---|---|
expression of His6-tagged p66/p51 HIV-1 reverse transcriptase p51/p66 52A variant C280S, the p66 subunit also contains the mutations K172A and K173A | Human immunodeficiency virus 1 |
Crystallization (Comment) | Organism |
---|---|
purified p66/p51 HIV-1 reverse transcriptase 52A variant in complex with inhibitors manicol and TMC278, 0.0012 ml of 20 mg/mL protein in 9.2 mM Tris, pH 8.0, 68.7 mM NaCl, 3.6 mM manganese sulfate, 0.7 mM tris(2-carboxyethyl) phosphine, 0.27% w/v, beta-ocytl glucopyranoside, 7% v/v DMSO, 0.9 mM manicol, and 0.7 mM TMC278, mixed with 0.0012 ml of reservoir solution containing 50 mM HEPES pH 7.5, 100 mM ammonium sulfate, 15 mM manganese sulfate, 10 mM spermine, 5 mM TCEP, and 11% w/w PEG 8000, X-ray diffraction structure determination and analysis at 2.7 A resolution, modeling | Human immunodeficiency virus 1 |
Protein Variants | Comment | Organism |
---|---|---|
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 | Human immunodeficiency virus 1 |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2S)-5,7-dihydroxy-2-(2-hydroxy-1-(phenylsulfonyl)propan-2-yl)-9-methyl-3,4-dihydro-1H-benzo[7]annulen-6(2H)-one | - |
Human immunodeficiency virus 1 | |
1,3,4,5-tetrahydrogalloylapitol | - |
Human immunodeficiency virus 1 | |
2,7-dihydroxy-4-isopropyl-cyclohepta-2,4,6-triene | i.e. beta-thujaplicinol | Human immunodeficiency virus 1 | |
2-(1,2-dihydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-(2-benzylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-(2-ethanesulfonyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-(2-ethylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
2-[2-(2-fluoro-benzylamino)-1-hydroxy-1-methyl-ethyl]-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
3,9,11,14,15-pentahydroxy-7-methoxy-10-methyl-5,6-dihydrobenzo[9,10]tetrapheno[2,3-c]furan-1,8,13(3H)-trione | - |
Human immunodeficiency virus 1 | |
4-[[4-([4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl]amino)pyrimidin-2-yl]amino]benzonitrile | i.e. TMC278 or rilpivirine, enzyme-bound structure, overview | Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylaminoethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylsulfanylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-(1-hydroxy-ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | - |
Human immunodeficiency virus 1 | |
5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | i.e. manicol, the alpha-hydroxytroplone potently and specifically inhibits HIV RT ribonuclease H, enzyme-bound structure, overview | Human immunodeficiency virus 1 | |
additional information | no inhibition by 5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, 5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, 2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one, and 2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | Human immunodeficiency virus 1 |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mn2+ | modeling of the HIV-1 RNase H domain in complex with an inhibitor and two Mn2+ cations from crystal structure of manicol-bound enzyme | Human immunodeficiency virus 1 |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Human immunodeficiency virus 1 | - |
HIV-1 | - |
Purification (Comment) | Organism |
---|---|
recombinant His6-tagged p66/p51 HIV-1 reverse transcriptase 52A variant C280S by nickel affinity chromatography, the tag is cleaved by HRV14 3C protease | Human immunodeficiency virus 1 |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | substrate is 18-nucleotide 3'-fluourescein-labeled RNA annealed to a complementary 18-nucleotide 5'-dabsyl-labeled DNA | Human immunodeficiency virus 1 | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | - |
Human immunodeficiency virus 1 |
Synonyms | Comment | Organism |
---|---|---|
human immunodeficiency virus reverse transcriptase-associated ribonuclease H | - |
Human immunodeficiency virus 1 |
ribonuclease H | - |
Human immunodeficiency virus 1 |
RNase H | - |
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 |
---|---|---|---|---|---|
0.00024 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(2-ethanesulfonyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00038 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(2-ethylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.0005 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(2-diethylamino-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00051 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | (2S)-5,7-dihydroxy-2-(2-hydroxy-1-(phenylsulfonyl)propan-2-yl)-9-methyl-3,4-dihydro-1H-benzo[7]annulen-6(2H)-one | |
0.00068 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 5,7-dihydroxy-2-(1-hydroxy-ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00082 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-piperidin-1-ylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00093 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylsulfanylethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00096 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(1-benzylamino-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.0012 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-[2-(2-fluoro-benzylamino)-1-hydroxy-1-methyl-ethyl]-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.0012 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 5,7-dihydroxy-2-(1-hydroxy-1-methyl-2-phenylaminoethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.0013 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(2-benzylsulfanyl-1-hydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.0019 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 2-(1,2-dihydroxy-1-methyl-ethyl)-5,7-dihydroxy-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one | |
0.00911 | - |
pH 8.0, 37°C | Human immunodeficiency virus 1 | 5,7-dihydroxy-2-(1-hydroxy-2-imadazol-1-yl-1-methyl ethyl)-9-methyl-1,2,3,4-tetrahydrobenzocyclohepten-6-one |