3OTS

MDR769 HIV-1 protease complexed with MA/CA hepta-peptide

Summary for 3OTS

• Entry DOI: 10.2210/pdb3ots/pdb
• Related: 3OTY 3OU1 3OU3 3OU4 3OUA 3OUB 3OUC 3OUD
• Descriptor: Multi-drug resistant HIV-1 protease, MA/CA substrate peptide (3 entities in total)
• Functional Keywords: mdr hiv-1 protease, inhibitor, drug resistance, substrate envelope, hiv-1 protease, protease, substrate peptide, hydrolase, hydrolase-peptide complex, hydrolase/peptide
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 22340.17

Authors

Liu, Z.,Wang, Y.,Brunzelle, J.,Kovari, I.A.,Kovari, L.C. (deposition date: 2010-09-13, release date: 2011-03-30, Last modification date: 2024-02-21)

Primary citation

Liu, Z.,Wang, Y.,Brunzelle, J.,Kovari, I.A.,Kovari, L.C.
Nine Crystal Structures Determine the Substrate Envelope of the MDR HIV-1 Protease.
Protein J., 30:173-183, 2011

PubMed Abstract: 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.

PubMed: 21394574
DOI: 10.1007/s10930-011-9316-2

Experimental method

X-RAY DIFFRACTION (1.7 Å)