CRYSTALLOGRAPHICS OF HIV &SIV PROTEASES IN COMPLEX W/ NON PEPTIDE INHIBITORS

$143,176P41FY2002RRNIH

Stanford University, Stanford CA

Investigators

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Abstract

HIV-1 PR crystallizes readily with a variety of inhibitors. We have determined enzyme/inhibitor complex structures from two crystal forms. One crystal form gives orthorhombic plates which diffract strongly to beyond 1.9 E. However, the other crystal form gives tetragonal bipyramids. These crystals are frequently no larger than 200 mm and diffract poorly using X-rays produced with our local equipment. The increased brilliance of a synchrotron source has produced diffraction to 2.5 E from these smaller crystals. The new SIV PR crystal complexes present the opportunity to determine enzyme/inhibitor structures unattainable with HIV PR. We anticipate to have 5-10 enzyme/inhibitor complex crystals ready thereby taking advantage of both the potential for rapid collection of datasets and increase in resolution.

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