3.4.23.47: HIV-2 retropepsin
This is an abbreviated version!
For detailed information about HIV-2 retropepsin, go to the full flat file.
Word Map on EC 3.4.23.47
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3.4.23.47
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polyproteins
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antiretroviral
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medicine
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darunavir
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saquinavir
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amprenavir
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lopinavir
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myeloblastosis
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nelfinavir
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hiv-2-infected
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drv
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drug development
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molecular biology
- 3.4.23.47
- polyproteins
-
antiretroviral
- medicine
- darunavir
- saquinavir
- amprenavir
- lopinavir
-
myeloblastosis
- nelfinavir
-
hiv-2-infected
- drv
- drug development
- molecular biology
Reaction
Endopeptidase for which the P1 residue is preferably hydrophobic =
Synonyms
HIV-2 protease, HIV-2 proteinase, human immunodeficiency virus 2 retropepsin, More, PR, PR2, retroviral aspartic proteinase, retroviral proteinase
ECTree
Advanced search results
Inhibitors
Inhibitors on EC 3.4.23.47 - HIV-2 retropepsin
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(2R,4S,5S)-6-cyclohexyl-5-(3,3-dimethylbutanamido)-4-hydroxy-2-isopropyl-N-((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)hexanamide
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synthetic inhibitor 4
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(4,6-dimethylpyrimidin-2-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
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hydroxyethylamine dipeptide isostere inhibitor 3
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethoxy)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
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hydroxyethylamine dipeptide isostere inhibitor 5
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
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hydroxyethylamine dipeptide isostere inhibitor 2
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-4-ylsulfonyl)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
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hydroxyethylamine dipeptide isostere inhibitor 4
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-4-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
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hydroxyethylamine dipeptide isostere inhibitor 1
benzyl (S)-1-((2S,3R)-4-((R)-4-(tert-butylcarbamoyl)thiazolidin-3-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-ylcarbamate
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synthetic inhibitor 1
benzyl (S)-1-((2S,3R)-4-((S) -2-(tert-butylcarbamoyl)indolin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-ylcarbamate
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synthetic inhibitor 2
H2O2
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inactivated after oxidation at the dimer interface, activity can be partly restored with methionine sulphoxide reductase
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethoxy)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
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hydroxyethylamine dipeptide isostere inhibitor 8
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
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hydroxyethylamine dipeptide isostere inhibitor 6
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
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hydroxyethylamine dipeptide isostere inhibitor 7
N-((S)-1-((2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)-octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-yl)quinoline-3-carboxamide
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synthetic inhibitor 3
tert-butyl (2S,3S)-5-(((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)carbamoyl)-1-cyclohexyl-3-hydroxy-6-methylheptan-2-ylcarbamate
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synthetic inhibitor 6
tert-butyl (2S,3S,5R)-5-(((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)carbamoyl)-1-cyclohexyl-3-hydroxy-6-methylheptan-2-ylcarbamate
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synthetic inhibitor 5
inhibitor binds less strongly to HIV-2 protease than to HIV-2 protease due to a reduction of the van der Waals interactions. Inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open
inhibitor binds less strongly to HIV-2 protease than to HIV-2 protease due to a reduction of the van der Waals interactions. Inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open
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n(2(R)hydroxy-1(S)indanyl)-5-((2(S)tertiarybutylaminocarbonyl)4(3pyridylmethyl)piperazino)-4(S)-hydroxy-2(R)-phenylmethylpentanamide, piperazino, L-735,524, potent orally bioavailable inhibitor, currently in a phase II clinical trial
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activity of lopinavir against three strains of HIV-2 is assessed and compared to activity against a reference HIV-1 strain. Lopinavir demonstrates activity similar to that observed against HIV-1 in two HIV-2 strains (HIV-2MS and HIV-2CBL-23) tested. 10fold reduced susceptibility is observed using strain HIV-2CDC310319
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no inhibition with 1,10-phenanthroline and phenylmethylsulfonylfluoride or EDTA
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additional information
analysis of the differences of binding patterns between the two type HIV proteases, HIV-1 protease and HIV-2 protease, and the two inhibitors darunavir and amprenavir using the interaction entropy (IE) method for the entropy change calculation combined with the polarized force field. The functional role of protonation states in the two HIV-2 complexes is investigated revealing that the protonated OD1 atom of Asp25' in B chain is the optimal choice. The bridging water W301 is unfavorable to the binding of HIV-2 complexes, in contrast to HIV-1 protease complexes. The volume of pocket, B-factor of Calpha atoms and the distance of flap tip in HIV-2 complexes are smaller than that of HIV-1 consistently. Predicated hot-spot residues (Ala28/Ala28', Ile50/Ile50', and Ile84/Ile84') are nearly same in the four systems. The contribution to the free energy of Asp30 residue is more favorable in HIV-1 system than in HIV-2 system. Molecular dynamics simulation and binding free energy calculations, and protonation states of the enzymes, overview
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additional information
comparison of 19 ligand-bound enzyme structures to localize structural asymmetry specific to particular ligands and the one conserved across most PR2 structures, detailed overview. Localization of structural variability induced by PR2 intrinsic flexibility
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additional information
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comparison of 19 ligand-bound enzyme structures to localize structural asymmetry specific to particular ligands and the one conserved across most PR2 structures, detailed overview. Localization of structural variability induced by PR2 intrinsic flexibility
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additional information
HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 protease inhibitors, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. Structural rationale for intrinsic HIV-2 PI resistance. No inhibition by amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, and tipranavir. Phenotypic protease inhibitor sensitivities of wild-type HIV-1, wild-type HIV-2, and mutant HIV-2 strains, overview
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additional information
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HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 protease inhibitors, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. Structural rationale for intrinsic HIV-2 PI resistance. No inhibition by amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, and tipranavir. Phenotypic protease inhibitor sensitivities of wild-type HIV-1, wild-type HIV-2, and mutant HIV-2 strains, overview
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additional information
HIV-2 protease (PR2) is naturally resistant to most FDA approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. Comparison of the HIV-1 protease (PR1) and HIV-2 protease (PR2) binding pockets extracted from structures complexed with 12 ligands, overview. Structural comparison of PR1 and PR2 pockets highlight structural changes induced by their sequence variations. PR2 pockets are more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. Specifically, substitutions at residues 31, 46, and 82 induce structural changes in their main-chain atoms that can affect PI binding in PR2. Substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which might underlie PR2 resistance against PIs
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additional information
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HIV-2 protease (PR2) is naturally resistant to most FDA approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. Comparison of the HIV-1 protease (PR1) and HIV-2 protease (PR2) binding pockets extracted from structures complexed with 12 ligands, overview. Structural comparison of PR1 and PR2 pockets highlight structural changes induced by their sequence variations. PR2 pockets are more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. Specifically, substitutions at residues 31, 46, and 82 induce structural changes in their main-chain atoms that can affect PI binding in PR2. Substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which might underlie PR2 resistance against PIs
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additional information
the ligand binding site is located at the interface between the two monomers and includes the catalytic triplet, Asp-Thr-Gly, conserved in all aspartic proteases. Detection of structural local asymmetry in the PR2 dimer complexed with a diversified set of ligands, quantification of the structural asymmetry of the PR2 set, overview
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additional information
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the ligand binding site is located at the interface between the two monomers and includes the catalytic triplet, Asp-Thr-Gly, conserved in all aspartic proteases. Detection of structural local asymmetry in the PR2 dimer complexed with a diversified set of ligands, quantification of the structural asymmetry of the PR2 set, overview
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