title: Statistical analysis of structural characteristics of protein Ca2+-binding sites.
abstract: To better understand the biological significance of Ca(2+), we report a comprehensive statistical analysis of calcium-binding proteins from the Protein Data Bank to identify structural parameters associated with EF-hand and non-EF-hand Ca(2+)-binding sites. Comparatively, non-EF-hand sites utilize lower coordination numbers (6 +/- 2 vs. 7 +/- 1), fewer protein ligands (4 +/- 2 vs. 6 +/- 1), and more water ligands (2 +/- 2 vs. 1 +/- 0) than EF-hand sites. The orders of ligand preference for non-EF-hand and EF-hand sites, respectively, were H(2)O (33.1%) > side-chain Asp (24.5%) > main-chain carbonyl (23.9%) > side-chain Glu (10.4%), and side-chain Asp (29.7%) > side-chain Glu (26.6%) > main-chain carbonyl (21.4%) > H(2)O (13.3%). Less formal negative charge was observed in the non-EF-hand than in the EF-hand binding sites (1 +/- 1 vs. 3 +/- 1). Additionally, over 20% of non-EF-hand sites had formal charge values of zero due to increased utilization of water and carbonyl oxygen ligands. Moreover, the EF-hand sites presented a narrower range of ligand distances and bond angles than non-EF-hand sites, possibly owing to the highly conserved helix-loop-helix motif. Significant differences between ligand types (carbonyl, side chain, bidentate) demonstrated that angles associated with each type must be classified separately, and the EF-hand side-chain Ca-O-C angles exhibited an unusual bimodal quality consistent with an Asp distribution that differed from the Gaussian model observed for non-EF-hand proteins. The results of this survey more accurately describe differences between EF-hand and non-EF-hand proteins and provide new parameters for the prediction and design of different classes of Ca(2+)-binding proteins.
authors.affiliation: Department of Chemistry, Center for Drug Design and Biotechnology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kirberger
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Hai
authors.initials: H
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Guantao
authors.initials: G
authors.lastname: Chen
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology; D008024:Ligands; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D008667:Metalloproteins; D002118:Calcium