Focusing of the electrostatic potential at EF-hands of calbindin D-9k: Titration of acidic residues

Citation
T. Kesvatera et al., Focusing of the electrostatic potential at EF-hands of calbindin D-9k: Titration of acidic residues, PROTEINS, 45(2), 2001, pp. 129-135
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
45
Issue
2
Year of publication
2001
Pages
129 - 135
Database
ISI
SICI code
0887-3585(20011101)45:2<129:FOTEPA>2.0.ZU;2-5
Abstract
Biological functions for a large class of calmodulin-related proteins, such as target protein activation and Ca2+ buffering, are based on fine-tuned b inding and release of Ca2+ ions by pairs of coupled EF-hand metal binding s ites. These are abundantly filled with acidic residues of so far unknown io nization characteristics, but assumed to be essential for protein function in their ionized forms. Here we describe the measurement and modeling of pK (a) values for all aspartic and glutamic acid residues in apo calbindin D-9 k, a representative of calmodulin-related proteins. We point out that while all the acidic residues are ionized predominantly at neutral pH, the onset of proton uptake by Ca2+ ligands with high pK(a) under these conditions ma y have functional implications. We also show that the negative electrostati c potential is focused at the bidental Ca2+ ligand of each site, and that t he potential is significantly more negative at the N-terminal binding site. (C) 2001 Wiley-Liss, Inc.