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Publication Abstract from PubMed

Identifying conserved pockets on the surfaces of a family of proteins can provide insight into conserved geometric features and sites of protein-protein interaction. Here we describe mapping and comparison of the surfaces of aligned crystallographic structures, using the protein kinase family as a model. Pockets are rapidly computed using two computer programs, FADE and Crevasse. FADE uses gradients of atomic density to locate grooves and pockets on the molecular surface. Crevasse, a new piece of software, splits the FADE output into distinct pockets. The computation was run on ten kinase catalytic cores aligned on the alphaF-helix, and the resulting pockets spatially clustered. The active site cleft appears as a large, contiguous site that can be subdivided into nucleotide and substrate docking sites. Substrate specificity determinants in the active site cleft between serine/threonine and tyrosine kinases are visible and distinct. The active site clefts cluster tightly, showing a conserved spatial relationship between the active site and alphaF-helix in the C-lobe. When the alphaC-helix is examined, there are multiple mechanisms for anchoring the helix using spatially conserved docking sites. A novel site at the top of the N-lobe is present in all the kinases, and there is a large conserved pocket over the hinge and the alphaC-beta4 loop. Other pockets on the kinase core are strongly conserved but have not yet been mapped to a protein-protein interaction. Sites identified by this algorithm have revealed structural and spatially conserved features of the kinase family and potential conserved inter- and intra-molecular binding sites.

Comparative surface geometry of the protein kinase family.,Thompson EE, Kornev AP, Kannan N, Kim C, Ten Eyck LF, Taylor SS Protein Sci. 2009 Jul 16. PMID:19610074^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.