From Protein Structure to Function with Bioinformatics.pdf

7 Predicting Protein Function from Surface Properties 173Fig. 7.2 PatchFinderPlus prediction. Shows the crystal structure of restriction endonuclease BglIprotein (spacefill) bound to its DNA (cartoon) recognition sequence (Newman et al. 1998). Thelargest positive electrostatic patch is shown in dark greyFor example, eF-Site (Kinoshita and Nakamura 2003) searches a database of surfacesdescribed in terms of their electrostatics and hydrophobic nature. A queryprotein can be searched against the most suitable database (antibody, active site,phosphate-binding site or a database derived from PROSITE definitions) and aselection of similar proteins are returned based only on their similarity to the surfaceof the query.7.3.3 Surface ConservationSurface conservation, as assessed by the ConSurf algorithm, has been instructive inpredicting the function of a number of proteins. One example involved an analysisof C-type lectin (CTLs) proteins that are presented on the outer surface of cells inorder to bind glycoproteins involved in immunity and endocytosis (Ebner et al.2003). CTLs have a very similar structure to the C-type lectin like domains (CTLDs)but the later cannot bind sugar moieties. ConSurf analysis of all domain memberswas useful in defining the conserved surface residues that define the CTL bindingsites. This conservation pattern was notably absent from CTLD structures. This disparitywas utilised to classify functionally unassigned CTL/CTLD domains.