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Overview for MACiE Entry M0175

Version history

General Information

EC Number: 3.4.23.16 (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).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

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Image of N-terminus of a protein

protein
C00017
CHEBI:36080
water
C00001
CHEBI:15377
C-terminus of a protein
X00073
CHEBI:33711
N-terminus of a protein
X00119
CHEBI:33712

Overall Comment: Structural kinetic and quantum chemical studies suggest that the most likely mechanism is that of general acid-general base catalysis [1].


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Stepwise Description of the Reaction

Step 1Asp25A deprotonates water, which then attacks the carbonyl carbon of the peptide bond in a nucleophilic addition, the resulting oxyanion then deprotonates Asp25B.
Step 2Asp25B 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

Type Number Chain Location of Function
Asp 25 A Side Chain
Gly 27 A Main Chain Amide
Asp 25 B Side Chain
Gly 27 B Main Chain Amide

References

  1. 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.
    Medline: 8780786
  2. S. Piana et al. (2002), J. Mol. Biol., 319, 567-583. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease.
    Medline: 12051929
  3. A. M. Silva et al. (1996), J. Mol. Biol., 255, 321-346. Inhibition and catalytic mechanism of HIV-1 aspartic protease.
    Medline: 8551523
  4. 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.
    Medline: 15066436

Homologue information for M0175 (1a30)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

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nucleic acid binding (molecular function)
DNA binding (molecular function)
RNA binding (molecular function)
catalytic activity (molecular function)
DNA-directed DNA polymerase activity (molecular function)
RNA-directed DNA polymerase activity (molecular function)
aspartic-type endopeptidase activity (molecular function)
nuclease activity (molecular function)
endonuclease activity (molecular function)
RNA-DNA hybrid ribonuclease activity (molecular function)
exoribonuclease H activity (molecular function)
structural molecule activity (molecular function)
nucleoplasm (cellular component)
cytosol (cellular component)
RNA-dependent DNA replication (biological process)
DNA recombination (biological process)
proteolysis (biological process)
metabolic process (biological process)
peptidase activity (molecular function)
zinc ion binding (molecular function)
integrase activity (molecular function)
DNA integration (biological process)
membrane (cellular component)
viral process (biological process)
transferase activity (molecular function)
nucleotidyltransferase activity (molecular function)
hydrolase activity (molecular function)
virion (cellular component)
viral capsid (cellular component)
()
initiation of viral infection (biological process)
uncoating of virus (biological process)
host cell plasma membrane (cellular component)
entry into host cell (biological process)
host cell cytoplasm (cellular component)
host cell membrane (cellular component)
host cell nucleus (cellular component)
interspecies interaction between organisms (biological process)
viral procapsid maturation (biological process)
metal ion binding (molecular function)
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