The Seattle Structural Genomics Center for Infectious Disease (http://ssgcid.org), is one of two Structural Genomics centers funded by NIAID to solve protein structures from organims causing infectious disease. Both Centers actively engage with infectious disease researchers to select Community Request (CR) targets for entry in their structure determination pipelines and to collaboratively interpret and publish results from successful structure determinations. SSGCID target selection focuses on essential enzymes, virulence factors, drug targets and vaccine candidates from numerous bacterial, eukaryotic, viral pathogens. In general, target genes are PCR amplified, cloned and screened for soluble expression in E. coli. Proteins are then purified in milligram amounts, screened for crystallization, and analyzed by X-ray diffraction using an in-house source or off-site synchrotron beam-line. Small proteins that fail to crystallize are queued for structure determination by NMR. Since project inception in late 2007, over 13,000 targets have entered the SSGCID structure determination pipeline, of which >5000 are CRs, resulting in deposition of >850 protein structures in the Protein Data Bank (PDB), including >400 from targets requested by community researchers. In addition, more than 7800 expression clones and 3600 purified proteins are publicly available free of charge. Target-to-structure success rates vary considerably between genera (1-17%) and about one third of all SSGCID structures contain bound ligands. Each year ~25-50 High Value Targets (HVTs) from CRs enter several rescue pathways, including protein truncation or mutagenesis, selection of orthologues from related species, and use of yeast, baculovirus and/or mamammalian expression systems.
To-date, SSGCID has also initiated >60 Community Research Projects (CRPs) with collaborators from the scientific community. From these, three SSGCID-funded Functional (FUN) studies are undertaken each year, using structural data to guide hypothesis-driven experimental approaches aimed at elucidating the function of selected targets. We seek to actively engage investigators to utilize and integrate structural data into their research program, to nominate high-impact targets for structure determination and to collaborate on subsequent CRPs and FUN studies.
SSGCID is supported by US Federal Government Contract: HHSN272201200025C.