Structural genomics of infectious disease drug targets: the SSGCID

Abstract

The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five‐year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three‐dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug‐therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein‐expression systems, purified proteins, ligand screens and three‐dimensional structures produced by SSGCID constitute a valuable resource for drug‐discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high‐throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.

Crystal structures of Mycobacterial MeaB and MMAA-like GTPases

“…Concurrent with ligand co-crystallization experiments, we entered Rv1496 orthologs from closely related species into the SSGCID structure determination pipeline [20,21]. The ortholog strategy has proven successful previously [22].…”

Yeast-based systems for tropical disease drug discovery

“…Unfortunately, this approach does not warranty that picked-up compounds can have more than one non-identified target. [2] On the other hand, phenotypic screenings are cell-based assays that determine the ability of one compound either to kill or to prevent the proliferation of the pathogen. Phenotypic assays provide an unbiased approach to identify compounds that are active against the pathogen, but provide no information about the mechanism of action.…”

A Suite of Engineered GFP Molecules for Oligomeric Scaffolding

“…Ongoing efforts towards engineering proteins for improved crystallization stem from the generally low success rate and unpredictability of macromolecular crystallization (Sundstrom et al, 2006; Stacy et al, 2011). Regardless of the varied explanation for why many proteins are difficult to crystallize, the chances for a successful outcome might be improved by promoting the formation of intermolecular contacts that are compatible with crystal symmetry.…”