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Catalytic Site Atlas

CSA LITERATURE entry for 1a30

E.C. nameHIV-1 retropepsin
SpeciesHuman immunodeficiency virus 1 (Virus)
E.C. Number (IntEnz) 3.4.23.16
CSA Homologues of 1a30There are 440 Homologs
CSA Entries With UniProtID P04585
CSA Entries With EC Number 3.4.23.16
PDBe Entry 1a30
PDBSum Entry 1a30
MACiE Entry M0175

Literature Report

IntroductionHIV-1 protease is an essential part of the viral replication machinery, responsible for processing translated proteins into functional enzymes. It is part of the apartyl protease family. It cleaves the amide bond of proteins between non-specific pairs of residues.
MechansimEquivalent aspartate residues from each chain are involved in catalysis. In the first step, one acts as a base to deprotonate the nucleophilic water molecule, while the other acts as an acid to protonate the carbonyl group and activate it. In the second step, the acid/base roles are reversed. The carbonyl group is reformed and the C-N bond of the substrate is broken.
Both aspartate residues are required for catalytic activity. One must be protonated and the other deprotonated. Dissociation of the active dimeric form results in a complete loss of activity. Note that since this is a homodimer the assignment of chains A and B is arbitrary.
Thr26/Thr26' and Gly27/Gly27' have previously been implicated in the catalytic mechanism. However, they are more likely to be involved in stabilising the active site (Thr26/Thr26') and positioning the substrate (Gly27/Gly27').

Catalytic Sites for 1a30

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA25513macie:sideChainDeprotonates the nucleophilic water molecule in the first step; protonates the leaving group in the second step.
AspB25513macie:sideChainProtonates the carbonyl in the first step; deprotonates the resulting alcohol in the second step.

Literature References

Notes:
Liu H
A combined quantum/classical molecular dynamics study of the catalytic mechanism of HIV protease.
J Mol Biol 1996 261 454-469
PubMed: 8780786
Mager PP.
The active site of HIV-1 protease.
Med Res Rev 2001 21 348-353
PubMed: 11410934
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