Two new inhibitor binding sites were discovered on wild-type HIV protease using fragment-based screening techniques. Protease was cocrystallized or soaked with chemical fragments using five different crystal forms, and 378 data sets were collected. Fragment binding induces a new conformation and crystal form in protease with the active site inhibitor TL-3. This study is the first fragment-based crystallographic screen against HIV protease, revealing two new exosites that stabilize inhibitor binding at the active site.
A. L. Perryman, Q. Zhang, H. H. Soutter, R. Rosenfeld, D. E. McRee, A. J. Olson, J. E. Elder & C. D. Stout (2010) Chem Biol. Drug Des. 75, 257-268.
Pubmed PMID: 20659109
Pubmed Central PMCID: PMC2911974