HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 18, 12393-12401, May 2, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/18/12393    most recent M707434200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Moya-García, A. A. Articles by Tuñón, I. PubMed PubMed Citation Articles by Moya-García, A. A. Articles by Tuñón, I. Social Bookmarking                      What's this?

Analysis of the Decarboxylation Step in Mammalian Histidine Decarboxylase

A COMPUTATIONAL STUDY^*

Aurelio A. Moya-García, Supported by a Junta de Andalucía doctoral fellowship¹, Javier Ruiz-Pernía², Sergio Martí^¶, Francisca Sánchez-Jiménez, and Iñaki Tuñón³

From the Procel Laboratory, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus Teatinos, 29071 Málaga, Spain and CIBERER, 46010 València, Spain, Departamento de Química Física, Universitat de València, Burjassot, 46100 València, Spain, and ^¶Departamento de Química-Física i Analítica, Universitat Jaume I, 12071 Castelló, Spain

We report a hybrid quantum mechanics/molecular mechanics theoretical study on the reaction mechanism of mammalian histidine decarboxylase that allows us to obtain valuable insights on the structure of the cofactor-substrate adduct (external aldimine) in the active site of rat histidine decarboxylase. By means of molecular dynamics simulations, we traced the potential of mean force corresponding to the decarboxylation reaction of the adduct both in the active site of the enzyme and in aqueous solution. By comparing this process in both media, we have identified the key electrostatic interactions that explain the lowering of the free energy barrier in the enzyme. Our analysis also offers a validation of Dunathan's hypothesis (Dunathan, H. (1966) Proc. Natl. Acad. Sci. U. S. A. 55, 712–716) regarding the role of stereoelectronic effects in the enzymatic decarboxylation process.

Received for publication, September 5, 2007 , and in revised form, January 28, 2008.

^* This work was supported in part by Ministerio de Educación y Ciencia Grants SAF2005-01812 and CTQ2006-15447-CO2-02 (Spain), Junta de Andalucía Grant CVI-267, Generalitat Valenciana Grant GV06-021, and the Fundación Ramón Areces. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

² Supported by a Ministerio de Educacion y Ciencia doctoral fellowship.

¹ To whom correspondence may be addressed. E-mail: amoyag{at}uma.es. ³ To whom correspondence may be addressed. E-mail: Tunon{at}uv.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?