The carboxylate shift in zinc enzymes: A computational study

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Sergio F Sousa (Author) Other; Pedro A Fernandes (Author) FCUP; Maria Joao Ramos (Author) FCUP

Journal

Title: Journal of the American Chemical Society

Vol. 129 No. 50

Pages: 1378-1385

ISSN: 0002-7863

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 122 Citations

Scopus - 125 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-004-BV5

DOI: 10.1021/ja067103n

Abstract (EN): Zinc is the second most abundant transition element in biology and the only metal known to be represented in enzymes from each one of the six classes established by the International Union of Biochemistry. The flexible coordination geometry, the fast ligand exchange, the lack of redox activity, and its role as Lewis acid are just some of the features that make zinc an invaluable element in biological catalysis. In this study, we have analyzed the importance in mononuclear Zn enzymes of an interesting mechanistic phenomenon known as carboxylate shift, which is characterized by a change in the coordination mode of a carboxylate group (mono to bidentate or vice versa) with both ligand entrance or exit from the metal coordination sphere. Using B3LYP calculations, we were able to unveil in detail patterns relating the intrinsic characteristics of a given Zn coordination sphere with the existence or not of a carboxylate-shift mechanism and the additional energy stabilization arising from it. In particular, a specific Zn coordination sphere containing a carboxylate ligand (Asp or Glu), a cysteine, and a histidine has been shown to have the most favorable combination of amino acid residues that ensures a fast ligand exchange.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8