Determination of the Catalytic Pathway of a Manganese Arginase Enzyme Through Density Functional Investigation

被引：20

作者：

Leopoldini, Monica ^{[1
,2
]}

Russo, Nino ^{[1
,2
]}

Toscano, Marirosa ^{[1
,2
]}

机构：

[1] Univ Calabria, Dipartimento Chim, Ctr Eccellenza MIUR, I-87030 Arcavacata Di Rende, CS, Italy

[2] Univ Calabria, Ctr Calcolo Ad Alte Prestaz Elaboraz Parallele &, Ctr Eccellenza MIUR, I-87030 Arcavacata Di Rende, CS, Italy

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2009年 / 15卷 / 32期

关键词：

arginase; catalytic mechanism; density functional calculations; metalloenzymes; transition states; EFFECTIVE CORE POTENTIALS; POLARIZABLE CONTINUUM MODEL; MOLECULAR-ORBITAL METHODS; NITRIC-OXIDE SYNTHASE; GAUSSIAN-TYPE BASIS; RAT-LIVER ARGINASE; AB-INITIO; ORNITHINE-DECARBOXYLASE; ARGININE METABOLISM; ORGANIC-MOLECULES;

D O I：

10.1002/chem.200802252

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The catalytic mechanism of dimanganese-containing arginase enzyme has been investigated by DFT calculations. Two exchange-correlation functionals, B3LYP and MPWB1 K, have been used to construct the potential energy profiles for the hydrolysis of an arginine substrate performed by an arginase active site model system. Two reaction mechanisms have been investigated. one involving a water molecule (mechanism 1) and the other involving a hydroxide ion (mechanism 2) as nucleophilic agent. Results obtained in the gas phase and in the protein environment have indicated that mechanism 1 involving a water molecule entails structural features as well as an activation energy for the rate-determining step that are inconsistent with experimental data available for the arginase enzyme. On the other hand, when a hydroxide ion is present at the Mn2 site, a lower activation energy and a structural arrangement closer to the experimental indication are obtained.

引用

页码：8026 / 8036

页数：11

共 60 条

[51] INTERACTION BETWEEN ARGINASE AND L-ORNITHINE CARBAMOYLTRANSFERASE IN SACCHAROMYCES-CEREVISIAE - PURIFICATION OF S-CEREVISIAE ENZYMES AND EVIDENCE THAT THESE ENZYMES AS WELL AS RAT-LIVER ARGINASE ARE TRIMERS [J].