Document Detail


A DFT study of the mechanism of Ni superoxide dismutase (NiSOD): role of the active site cysteine-6 residue in the oxidative half-reaction.
MedLine Citation:
PMID:  16804959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present DFT study, the catalytic mechanism of H2O2 formation in the oxidative half-reaction of NiSOD, E-Ni(II) + O2- + 2H+ --> E-Ni(III) + H2O2, has been investigated. The main objective of this study is to investigate the source of two protons required in this half-reaction. The proposed mechanism consists of two steps: superoxide coordination and H2O2 formation. The effect of protonation of Cys6 and the proton donating roles of side chains (S) and backbones (B) of His1, Asp3, Cys6, and Tyr9 residues in these two steps have been studied in detail. For protonated Cys6, superoxide binding generates a Ni(III)-O2H species in a process that is exothermic by 17.4 kcal/mol (in protein environment using the continuum model). From the Ni(III)-O2H species, H2O2 formation occurs through a proton donation by His1 via Tyr9, which relative to the resting position of the enzyme is exothermic by 4.9 kcal/mol. In this pathway, a proton donating role of His1 residue is proposed. However, for unprotonated Cys6, a Ni(II)-O2- species is generated in a process that is exothermic by 11.3 kcal/mol. From the Ni(II)-O2- species, the only feasible pathway for H2O2 formation is through donation of protons by the Tyr9(S)-Asp3(S) pair. The results discussed in this study elucidate the role of the active site residues in the catalytic cycle and provide intricate details of the complex functioning of this enzyme.
Authors:
Rajeev Prabhakar; Keiji Morokuma; Djamaladdin G Musaev
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of computational chemistry     Volume:  27     ISSN:  0192-8651     ISO Abbreviation:  J Comput Chem     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-07-04     Completed Date:  2007-08-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9878362     Medline TA:  J Comput Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1438-45     Citation Subset:  IM    
Affiliation:
Cherry L. Emerson Center for Scientific Computation, and Department of Chemistry, Emory University, 1515 Dickey Dr., Atlanta, Georgia 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Binding Sites
Cysteine / chemistry*,  metabolism*
Models, Molecular
Nickel / chemistry,  metabolism*
Protein Conformation
Superoxide Dismutase / chemistry*,  metabolism*
Chemical
Reg. No./Substance:
52-90-4/Cysteine; 7440-02-0/Nickel; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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