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Title: First Principles Computational Study of the Active Site of Arginase

Abstract

Ab initio density functional theory (DFT) methods were used to investigate the structural features of the active site of the binuclear enzyme rat liver arginase. Special emphasis was placed on the crucial role of the second shell ligand interactions. These interactions were systematically studied by performing calculations on models of varying size. It was determined that a water molecule, and not hydroxide, is the bridging exogenous ligand. The carboxylate ligands facilitate the close approach of the Mn (II) ions by attenuating the metal-metal electrostatic repulsion. Of the two metals, MnA was shown to carry a larger positive charge. Analysis of the electronic properties of the active site revealed that orbitals involving the terminal Asp234 residue, as well as the flexible -1,1 bridging Asp232, lie at high energies, suggesting weaker coordination. This is reflected in certain structural variability present in our models and is also consistent with recent experimental findings. Finally, implications of our findings for the biological function of the enzyme are delineated.

Authors:
;
Publication Date:
Research Org.:
Pacific Northwest National Lab., Richland, WA (US), Environmental Molecular Sciences Laboratory (US)
Sponsoring Org.:
US Department of Energy (US)
OSTI Identifier:
15006951
DOE Contract Number:
AC06-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proteins; Journal Volume: 54; Journal Issue: 1; Other Information: PBD: 14 Jan 2004
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ARGINASE; BIOLOGICAL FUNCTIONS; ELECTROSTATICS; ENZYMES; FUNCTIONALS; LIVER; WATER; ENVIRONMENTAL MOLECULAR SCIENCES LABORATORY, NULL

Citation Formats

Ivanov, Ivaylo, and Klien, Micheal. First Principles Computational Study of the Active Site of Arginase. United States: N. p., 2004. Web. doi:10.1002/prot.10572.
Ivanov, Ivaylo, & Klien, Micheal. First Principles Computational Study of the Active Site of Arginase. United States. doi:10.1002/prot.10572.
Ivanov, Ivaylo, and Klien, Micheal. 2004. "First Principles Computational Study of the Active Site of Arginase". United States. doi:10.1002/prot.10572.
@article{osti_15006951,
title = {First Principles Computational Study of the Active Site of Arginase},
author = {Ivanov, Ivaylo and Klien, Micheal},
abstractNote = {Ab initio density functional theory (DFT) methods were used to investigate the structural features of the active site of the binuclear enzyme rat liver arginase. Special emphasis was placed on the crucial role of the second shell ligand interactions. These interactions were systematically studied by performing calculations on models of varying size. It was determined that a water molecule, and not hydroxide, is the bridging exogenous ligand. The carboxylate ligands facilitate the close approach of the Mn (II) ions by attenuating the metal-metal electrostatic repulsion. Of the two metals, MnA was shown to carry a larger positive charge. Analysis of the electronic properties of the active site revealed that orbitals involving the terminal Asp234 residue, as well as the flexible -1,1 bridging Asp232, lie at high energies, suggesting weaker coordination. This is reflected in certain structural variability present in our models and is also consistent with recent experimental findings. Finally, implications of our findings for the biological function of the enzyme are delineated.},
doi = {10.1002/prot.10572},
journal = {Proteins},
number = 1,
volume = 54,
place = {United States},
year = 2004,
month = 1
}
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