STRUCTURE AND FUNCTION OF RETROVIRAL PROTEASES

The need to develop safe and effective therapies for the treatment of AIDS has stimulated many groups to study the retroviral proteases, particularly the protease from HIV-1. Research reports appear seemingly daily, and a review of this nature is necessarily outdated before it is published. From a crystallographic perspective, a conservative estimate is that more than twenty structures of inhibited complexes of HIV-1 protease have been examined to date, although only three have been published as of this writing. This enzyme will be studied by a larger number of independent investigators, in a greater variety of crystalline modifications, and with a greater variety of ligands than has ever been the case for an enzyme before. This wealth of structural information will provide an unprecedented opportunity for assessing the contributions of various protein-ligand interactions (hydrogen bonds, van der Waals interactions, etc) to observed inhibition constants, for studying the structural plasticity of the enzyme itself, and for examining the effect of crystal packing forces on protein conformation.