Coordination contributions to protein stability in metal-substituted carbonic anhydrase

By George P. Lisi, Russell P. Hughes, Dean E. Wilcox

July 28, 2017

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Title

Coordination contributions to protein stability in metal-substituted carbonic anhydrase

Author

George P. Lisi, Russell P. Hughes, Dean E. Wilcox

Year

2016

Journal

Journal of Biological Inorganic Chemistry

Abstract

Contributions of the active site metal to the stability of carbonic anhydrase (CA) were quantified by differential scanning calorimetry and complementary unfolding measurements of CA substituted with Co2+, Cd2+, Cu2+, Ni2+ and Mn2+. The metal ions stabilize the protein to different extent, with the highest stability provided by the native Zn2+. This additional stability does not correlate with the enthalpy of the three metal-imidazole (His) bonds at the active site or other properties of the metal ions (charge density, hydration enthalpy). However, DFT calculations reveal an energetic penalty associated with metal coordination at the active site, and the magnitude of this penalty correlates inversely with metal contributions to the stability of the protein. While the affinity of CA for metal ions generally reflects the Irving–Williams series, the additional thermal stability provided by metal ions is modulated by the rigid His3 coordination that is imposed at the protein site.

Full Article

http://link.springer.com/article/10.1007/s00775-016-1375-6

Instrument

J-815

Keywords

Circular dichroism, Secondary structure, Ligand binding, Protein folding, Protein denaturation, Thermodynamics, Biochemistry