Structural genomics consortium

Rupp, B., Segelke, B.W., Krupka, H.I., Lekin, T., Shafer, J., Zemla, A., Topani, D., SneU, G., and Earnest, G. (2002).The TB structural genomics consortium crystallization facility towards automation from protein to electron density. Acta Crystallogr. D 58, 1514-1518. 

Advancements in crystallography/NMR techniques have resulted in an exponential increase in the number of protein structures in publicly available structural databases (e.g., as of September 2009, the Protein Database Bank PDB contains experimentally solved 3D structural data for 60,000 structures (www.pdb.org)). In addition, several structural genomics consortiums aim to provide crystal structures across all protein families (38). In case when experimental structures are not available, techniques such as homology modeling are often used to build structural models of other homologous proteins (21). 

Doyle, D. A., Oppermann, U. C., Sund-strom, M. (2007) The scientific impact of the Structural Genomics Consortium a protein family and ligand-centered approach to medically-relevant human proteins. J Struct Funct Genomics 8, 107-119. 

Fig. 6. Structure of the animal FAS. (A) An overview of the entire complex (reproduced with permission of Maier et al. [9]). Fitted homologous domains are shown with a semi-transparent surface representation of the experimental 4.5-A-resolution electron density. Two white stars indicate the pseudosymmetry-related suggested attachment regions for the ACP and thioesterase ACP and TE, where more density is visible on the right side. MAT, malonyl/acetyltransferase. (B) High-resolution structures of the ACP and MAT domains (Structural Genomics Consortium) and the TE domain (F.A. Quiocho, 2004) of the human FAS showing locations of active-site residues. The gray region of the MAT (residues 422-484) represents a structured linker region that probably interacts with the adjacent KS domain and is not part of the MAT catalytic domain. (See color plate section, plate no. 5.)...

Most prokaryotes employ dedicated PPTs active toward specific apoprotein substrates. Fungi also utilize separate PPTs for modification of the ACPs associated with the cytosolic and mitochondrial FAS systems, as well as the a-aminoadipate reductase involved in lysine biosynthesis [8]. The former is unusual in that it is a constituent domain of the multifunctional a-subunit (Fig. 4). Surprisingly, animals appear to employ a single PPT for servicing three different apoproteins the ACP domain of the cytosolic FAS, the ACP component of the mitochondrial FAS, and the a-aminoadipate semialdehyde dehydrogenase involved in lysine catabolism. The human PPT has recently been identified and characterized (S. Smith, 2003) and its crystal structure determined in complex with Mg, CoA, and the ACP domain of the cytosolic FAS (Structural Genomics Consortium). The ACP domain is comprised of a four-helix bundle, as are the ACPs associated with type II systems. The conserved serine residue that is the site of posttranslational modification lies at the N-terminal end of helix-2 (Fig. 6B), closely juxtaposed with the pyrophosphate of CoA that is cleaved during the phosphopantetheine transfer. Helix-2 makes multiple... 

Recently, several of the components of a putative type II FAS system have also been identified in human mitochondria, including ACP, malonyltransferase, KS (S. Smith, 2003, 2005), and ER (J.K. Hiltunen, 2003). All are nuclear encoded and possess aminoterminal extension sequence elements that target the proteins into mitochondria. The mitochondrial ACP is phosphopantetheinylated by the same enzyme that services the ACP domain of the cytosolic FAS, presumably prior to import into the mitochondria. The crystal structures of all of these enzymes have been solved (Structural Genomics Consortium, J.K. Hiltunen,... 

Joint Center for Structural Genomics Berkeley Structural Genomics Center TB Structural Genomics Consortium Ontario Cancer Institute/University of Toronto/Pacific Northwest National Laboratory/University of British Columbia/McGill University Center for Advanced Research in... 

I thank all members of the North East Structural Genomics Consortium, but especially my collaborator at Yale, Mark Gerstein, for his insights and advice on illustrations for my presentation. I acknowledge Christine Orenga and Janet Thornton for the CATH protein classification system and for the illustrations in this article that are taken from their work. 

Structural Genomics Consortium and Target Discovery Institute Roosevelt Drive Oxford 0X3 7FZ UK... 

Mansfield Road, Oxford, UK, 0X1 3TA Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, UK, 0X3 7DQ... 

Morgan Jones, M., Castle-Clarke, S., Brooker, D., Nason, E., Huzair, F. Chataway, J. (2014) The Structural Genomics Consortium A knowledge platform for drug discovery, A RAND research report. Availahle from http //www.rand.org/pubs/ research reports/RR512.html [accessed 1 May 2015). 

Aled M. Edwards is in the Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, Chas Bountra is in die Structural Genomics Consortium, University of Oj ord, Headington, Oj ord, UK,... 

D. Dodds, S. Fiye, B. Gieenbeig, J. Wei gelt, H.Widmei,T.Yamada and R. Young for comments on the paper. A.M.E. and C.B. are supported by the Structural Genomics Consortium, which is a registered charity (number 1097737) that receives... 

---