From Genome to Life:

HOL Wim

HHMI & Univ. of Washington, Health Science Bldg., Room K-428, Box 357742, Seattle, WA 98195, USA

title: Medicinal protein crystallography and structural genomics for tropical diseases

First, an overview will be given of work, together with numerous collaborators, on crystal structures from key proteins from tropical pathogens illustrating the value of knowing the three-dimensional structure of target proteins for the design of novel inhibitors. Topics to be discussed are the degree of similarity between pathogen and human homologues, conformational changes induced by designed inhibitors (some inhibitors apparently dig their own hole) and the use of anomalous scattering for precisely determining ligand binding modes. Second, a description will be given of the recently funded NIH project "Structural Genomics of Pathogenic Protozoa (SGPP)". The SGPP Consortium comprises groups at the University of Washington, Seattle; the Seattle Biomedical Research Institute: the ALS, UC Berkeley, and SSRL, Stanford, synchrotrons; The Hauptman Woodward Institute in Buffalo NY and the University of Rochester, NY. The goals are to solve a large number of water soluble proteins as well as a number of membrane proteins and protein-protein complexes. Strategies and approaches will be outlined. All structures solved will be made publicly available and suggestions from the scientific community to strengthen this project will be very welcome. SGPP focuses on Trypanosoma brucei, T. cruzi, Leishmania major and related species, and Plasmodium falciparum.