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Literature summary extracted from

  • Triki, D.; Billot, T.; Visseaux, B.; Descamps, D.; Flatters, D.; Camproux, A.C.; Regad, L.
    Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases (2018), Sci. Rep., 8, 5789 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.4.23.16 medicine the HIV proteases are effective therapeutic targets for treating HIV infection because of the essential role in hydrolysing the viral Gag and Gag-Pol precursor polyprotein during infectious viral particle maturation Human immunodeficiency virus 1
3.4.23.47 medicine the HIV proteases are effective therapeutic targets for treating HIV infection because of the essential role in hydrolysing the viral Gag and Gag-Pol precursor polyprotein during infectious viral particle maturation Human immunodeficiency virus 2

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.23.16 HIV protease PR1, sequence comparisons with PR2 Human immunodeficiency virus 1
3.4.23.47 HIV protease PR2, sequence comparisons with PR1 Human immunodeficiency virus 2

Protein Variants

EC Number Protein Variants Comment Organism
3.4.23.16 C67A naturally occuring mutation Human immunodeficiency virus 1
3.4.23.16 C95A naturally occuring mutation Human immunodeficiency virus 1
3.4.23.16 L33I naturally occuring mutation Human immunodeficiency virus 1
3.4.23.16 L63I naturally occuring mutation Human immunodeficiency virus 1
3.4.23.16 L76M site-directed mutagenesis, mutant enzyme structure modelling Human immunodeficiency virus 1
3.4.23.16 additional information modelling of PR1 mutant structures containing V32I and L76M substitutions reveals a cooperative mechanism leading to structural deformation of flap-residue 45 that can modify PR2 flexibility Human immunodeficiency virus 1
3.4.23.16 Q7K naturally occuring mutation Human immunodeficiency virus 1
3.4.23.16 V32I site-directed mutagenesis, mutant enzyme structure modelling Human immunodeficiency virus 1

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.23.16 additional information 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. Modelling of PR1 mutant structures containing V32I and L76M substitutions reveals a cooperative mechanism leading to structural deformation of flap-residue 45 that can modify PR2 flexibility. Substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which might underlie PR2 resistance against PIs Human immunodeficiency virus 1
3.4.23.47 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 Human immunodeficiency virus 2

Organism

EC Number Organism UniProt Comment Textmining
3.4.23.16 Human immunodeficiency virus 1 P04587 Gag-Pol polyprotein; HIV-1
-
3.4.23.47 Human immunodeficiency virus 2 P04584 Gag-Pol polyprotein; HIV-2
-

Synonyms

EC Number Synonyms Comment Organism
3.4.23.16 HIV-2 protease
-
 Human immunodeficiency virus 1
3.4.23.16 PR2
-
 Human immunodeficiency virus 1
3.4.23.47 HIV-2 protease
-
 Human immunodeficiency virus 2
3.4.23.47 PR2
-
 Human immunodeficiency virus 2

General Information

EC Number General Information Comment Organism
3.4.23.16 evolution HIV proteases PR1 and PR2 share only approximately 50% of sequence identity but they exhibit a similar global fold Human immunodeficiency virus 1
3.4.23.16 additional information comparison of the HIV-1 protease and HIV-2 protease binding pockets extracted from structures complexed with 12 ligands, overview Human immunodeficiency virus 1
3.4.23.47 evolution HIV proteases PR1 and PR2 share only approximately 50% of sequence identity but they exhibit a similar global fold Human immunodeficiency virus 2
3.4.23.47 additional information comparison of the HIV-1 protease and HIV-2 protease binding pockets extracted from structures complexed with 12 ligands, overview Human immunodeficiency virus 2