Abstract
AbstractWhy metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 Å) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference54 articles.
1. Lippard, S. J. & Berg, J. M. Principles of Bioinorganic Chemistry 70 (University Science Books Mill Valley, CA, 1994).
2. Holm, R. H., Kennepohl, P. & Solomon, E. I. Structural and functional aspects of metal sites in biology. Chem. Rev. 96, 2239–2314 (1996).
3. Ragsdale, S. W. Metals and their scaffolds to promote difficult enzymatic reactions. Chem. Rev. 106, 3317–3337 (2006).
4. Liu, J. et al. Metalloproteins containing cytochrome, iron-sulfur, or copper redox centers. Chem. Rev. 114, 4366–4469 (2014).
5. Rulisek, L. & Vondrasek, J. Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins. J. Inorg. Biochem. 71, 115–127 (1998).
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