Statistical analysis of structural characteristics of protein Ca2+-binding sites

• Published in: Journal of biological inorganic chemistry Vol. 13; no. 7; pp. 1169 - 1181
• Main Authors: Kirberger, Michael, Wang, Xue, Deng, Hai, Yang, Wei, Chen, Guantao, Yang, Jenny J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.09.2008
• Subjects: Binding Sites; Biochemistry; Biomedical and Life Sciences; Calcium - chemistry; Calcium - metabolism; Computational Biology; Life Sciences; Ligands; Metalloproteins - chemistry; Metalloproteins - metabolism; Microbiology; Models, Molecular; Original Paper; Protein Binding; Protein Conformation; Calcium binding; Structure; Metalloprotein; EF-hand; Prediction
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-008-0402-7

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.