computational modeling of the mechanism of urease脲酶的机理的计算模型.pdfVIP

Hindawi Publishing Corporation Bioinorganic Chemistry and Applications Volume 2010, Article ID 364891, 8 pages doi:10.1155/2010/364891 Research Article Computational Modeling of the Mechanism of Urease ˚ Hakan Carlsson and Ebbe Nordlander Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, Box 124, 221 00 Lund, Sweden Correspondence should be addressed to Ebbe Nordlander, ebbe.nordlander@chemphys.lu.se Received 9 April 2010; Accepted 31 May 2010 Academic Editor: Spyros P. Perlepes Copyright © 2010 H. Carlsson and E. Nordlander. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In order to elucidate aspects of the mechanism of the hydrolytic enzyme urease, theoretical calculations were undertaken on a model of the active site, using density functional theory. The bridging oxygen donor that has been found in the crystal structures was determined to be a hydroxide ion. The initial coordination of urea at the active site occurs most likely through the urea oxygen to the nickel ion with the lowest coordination number. This coordination can be made without much gain in energy. The calculations also showed that weak coordination of one of the urea amine nitrogen atoms to the second nickel atom is energetically feasible. Furthermore, a proposed mechanism including a tetrahedral intermediate generated by hydrolytic attack on the urea carbon by the bridging hydroxide was modeled, and the tetrahedral intermediate was found to be energetically unfavorable relative to terminal coordination of the substrate (urea). 1. Introduction