Structural Bioinformatics, 2nd Edition

40

STRUCTURAL GENOMICS OF PROTEIN SUPERFAMILIES

Stephen K. Burley, Steven C. Almo, Jeffrey B. Bonanno, Mark R. Chance, Spencer Emtage, Andras Fiser, Andrej Sali, J. Michael Sauder, and Subramanyam Swaminathan

Under the auspices of the National Institutes of Health (NIH)—National Institute of General Medical Sciences (NIGMS) Protein Structure Initiative (PSI), the New York SGX Research Center for Structural Genomics (NYSGXRC) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of two large protein superfamilies. Approximately, 15% of consortium resources are devoted to structural studies of protein phosphatases, which are classified as Biomedical Theme targets. A further ~ 15% of effort is devoted to structural studies of enolases (ENs) and amidohydrolases (AHs) as community-nominated targets. NYSGXRC efforts with the protein phosphatases have, to date, yielded structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcription regulation, signal transduction, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise ...