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Analysis and prediction of calcium‐binding pockets from apo‐protein structures exhibiting calcium‐induced localized conformational changes
Author(s) -
Wang Xue,
Zhao Kun,
Kirberger Michael,
Wong Hing,
Chen Guantao,
Yang Jenny J.
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.394
Subject(s) - chemistry , side chain , crystallography , calcium , protein structure , conformational change , ligand (biochemistry) , calcium binding protein , binding site , stereochemistry , biophysics , biochemistry , receptor , biology , organic chemistry , polymer
Calcium binding in proteins exhibits a wide range of polygonal geometries that relate directly to an equally diverse set of biological functions. The binding process stabilizes protein structures and typically results in local conformational change and/or global restructuring of the backbone. Previously, we established the MUG program, which utilized multiple geometries in the Ca 2+ ‐binding pockets of holoproteins to identify such pockets, ignoring possible Ca 2+ ‐induced conformational change. In this article, we first report our progress in the analysis of Ca 2+ ‐induced conformational changes followed by improved prediction of Ca 2+ ‐binding sites in the large group of Ca 2+ ‐binding proteins that exhibit only localized conformational changes. The MUG SR algorithm was devised to incorporate side chain torsional rotation as a predictor. The output from MUG SR presents groups of residues where each group, typically containing two to five residues, is a potential binding pocket. MUG SR was applied to both X‐ray apo structures and NMR holo structures, which did not use calcium distance constraints in structure calculations. Predicted pockets were validated by comparison with homologous holo structures. Defining a “correct hit” as a group of residues containing at least two true ligand residues, the sensitivity was at least 90%; whereas for a “correct hit” defined as a group of residues containing at least three true ligand residues, the sensitivity was at least 78%. These data suggest that Ca 2+ ‐binding pockets are at least partially prepositioned to chelate the ion in the apo form of the protein.