3OU3: Mdr769 Hiv-1 Protease Complexed With PrRT HEPTA-Peptide

Under drug selection pressure, emerging mutations render HIV-1 protease drug resistant, leading to the therapy failure in anti-HIV treatment. It is known that nine substrate cleavage site peptides bind to wild type (WT) HIV-1 protease in a conserved pattern. However, how the multidrug-resistant (MDR) HIV-1 protease binds to the substrate cleavage site peptides is yet to be determined. MDR769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) was selected for present study to understand the binding to its natural substrates. MDR769 HIV-1 protease was co-crystallized with nine substrate cleavage site hepta-peptides. Crystallographic studies show that MDR769 HIV-1 protease has an expanded substrate envelope with wide open flaps. Furthermore, ligand binding energy calculations indicate weaker binding in MDR769 HIV-1 protease-substrate complexes. These results help in designing the next generation of HIV-1 protease inhibitors by targeting the MDR HIV-1 protease.
PDB ID: 3OU3Download
MMDB ID: 89532
PDB Deposition Date: 2010/9/14
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3OU3: trimeric; determined by author and by software (PISA)
Molecular Components in 3OU3
Label Count Molecule
Proteins (3 molecules)
Hiv-1 Protease
Molecule annotation
Pr/rt Substrate Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB