From Protein Structure to Function with Bioinformatics.pdf

150 B.H. Dessailly and C.A. OrengoFig. 6.1 Supersites in the (β/α) 8TIM-like barrel fold. Cartoon illustrations of four proteins adoptingthe (β/α) 8barrel fold, which have been classified in different CATH (and SCOP) superfamilies:(a) E. coli Dihydropteroate Synthase (CATH domain ID: 1aj0A00), (b) P. furiosus TryptophanSynthase alpha-subunit (CATH domain ID: 1geqB00), (c) C. thermocellum Endo-1,4-beta-xylanaseZ (CATH domain ID: 1xyzA00), and (d) H. sapiens Aldehyde Reductase (CATH domain ID:2alrA00). The four structures have been superposed using CORA (Orengo 1999). They are showninto a similar orientation, and common elements between the four structures are coloured in red.The positions of the catalytic residues in these four proteins (as defined in the Catalytic Site Atlas)are coloured green. In spite of major structural differences and the absence of evidence for homologybetween these proteins, the catalytic sites always locate around the C-terminal end of the coreβ-strands. Figures of three-dimensional structures were drawn using Molscript (Kraulis 1991) andrendered using Raster3D (Merritt and Bacon 1997)superfamilies (CATH v3.1), several of which are functionally diverse. Eventhough they represent a very small fraction of known folds, these superfolds seemto account for a disproportionate fraction of proteins in known genomes (Leeet al. 2005). Superfolds also cause a major problem for function prediction usingfold recognition since proteins sharing such a fold do not necessarily share thesame function. The existence of such folds and their considerable coverage of theprotein world has prompted caution regarding the usefulness of detecting foldrelationships for function prediction.