Analysis and prediction of calcium-binding pockets from apo-protein structures exhibiting calcium-induced localized conformational changes.
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.
Wang
Xue
X
Department of Computer Science, Georgia State University, Atlanta, Georgia 30303, USA.
Zhao
Kun
K
Kirberger
Michael
M
Wong
Hing
H
Chen
Guantao
G
Yang
Jenny J
JJ
D000465:Algorithms; D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D008958:Models, Molecular; D015233:Models, Statistical; D019906:Nuclear Magnetic Resonance, Biomolecular; D010320:Parvalbumins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
D001059:Apoproteins; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D010320:Parvalbumins; D001224:Aspartic Acid; D002118:Calcium