Overview for MACiE Entry M0175
EC Number: 22.214.171.124 (A member of the Hydrolases, Acting on peptide bonds (peptidases), Aspartic endopeptidases)
Enzyme Name: HIV-1 retropepsin
Biological Species: Human immunodeficiency virus type 1 (Virus)
Catalytic Chain UniprotKB Accession Codes:
Representative PDB Code: 1a30 - HIV-1 PROTEASE COMPLEXED WITH A TRIPEPTIDE INHIBITOR (Resolution = 2.00 Å).
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Overall Comment: Structural kinetic and quantum chemical studies suggest that the most likely mechanism is that of general acid-general base catalysis .
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Stepwise Description of the Reaction
|Step 1||Asp25A deprotonates water, which then attacks the carbonyl carbon of the peptide bond in a nucleophilic addition, the resulting oxyanion then deprotonates Asp25B.|
|Step 2||Asp25B deprotonates the alcohol group of the intermediate, initiating an elimination that cleaves the peptide bond. The N-terminal product then deprotonates Asp25A.|
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Catalytic Residues Involved
||Location of Function
||Main Chain Amide
||Main Chain Amide
- H. Liu et al. (1996), J. Mol. Biol., 261, 454-469. A combined quantum/classical molecular dynamics study of the catalytic mechanism of HIV protease.
- S. Piana et al. (2002), J. Mol. Biol., 319, 567-583. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease.
- A. M. Silva et al. (1996), J. Mol. Biol., 255, 321-346. Inhibition and catalytic mechanism of HIV-1 aspartic protease.
- Y. Tie et al. (2004), J. Mol. Biol., 338, 341-352. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains.
Homologue information for M0175 (1a30)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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