Reaction mechanism of the vitamin K-dependent glutamate carboxylase: A computational study

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

Authors

Pedro J Silva (Author) Other; Maria Joao Ramos (Author) FCUP

Journal

Title: Journal of Physical Chemistry B

Vol. 111

Pages: 12883-12887

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 12 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-004-6B2

DOI: 10.1021/jp0738208

Abstract (EN): In the reaction cycle of glutamate carboxylase, vitamin K epoxidation by O-2 has been proposed to generate a very strong base able to remove a proton from the gamma carbon of a Glu residue, thus yielding a Glu-based carbanion that readily reacts with CO2. We have used hybrid density functional theory to study this appealing mechanism. Our calculations show a very exergonic four-step mechanism with the reaction of (triplet) O-2 with the singlet vitamin K anion as the rate-limiting step, with a rate similar to the experimental value. Our study also establishes the need to apply continuum models when performing the optimization of minimum-energy crossing points between potential energy surfaces of different multiplicities for enzyme model systems.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5