Modeling the Transition State Structures of the Reductive-Half Reaction Active Site of Xanthine Oxidase Bound to Guanine Analogues: A Density Functional Theory Approach

Mamaru Bitew Alem and Yilkal Bezie Ayele

International Journal of Chemistry, 2018, vol. 10, issue 1, 137-152

Abstract: Modeling and characterization the transition state structure of enzyme catalyzed reactions is essential. A DFT method employing B3LYP level of theory with 6-31G (d',p') basis set for non-metals and LanL2DZ basis set for molybdenum have been used. The bond orders of chemical fragments were calculated using AOmix softaware. The effect of chalcogen replacement, amine group and methyl group in the parent structure of xanthine bound to xanthine oxidase active site were compared. The transition state structure of model substrates (2AX, 2A6TP, 2A6SP and 2A6MP) bound to the truncated form of XO active site has been confirmed by the presence of one negative imaginary frequencies (s-1) (-60), (-140), (-230) and (-270), respectively. The corresponding normalized energy barriers (kcal/mol) from pre-transition state to the transition state, respectively, are (13.869), (21.753), (23.109) and (0.212). In this work, 2A6SP and 2A6TP substrates were found to be potential xanthine oxidase inhibitors. The large bond distances and minimum bond order for CRH-HRH bond, and small bond distances and maximum bond order for SMo-HRH bond at the transition state for chalcogen replaced 2AX confirms early transition state structure. Methyl substituted 2AX analog found to have post transition state structure. A potential xanthine oxidase inhibitor can be designed from purine family enzymes using DFT approach.

Keywords: DFT; xanthine oxidase; modeling; stepwise mechanism; transition state (search for similar items in EconPapers)
Date: 2018
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
http://www.ccsenet.org/journal/index.php/ijc/article/download/73203/40248 (application/pdf)
http://www.ccsenet.org/journal/index.php/ijc/article/view/73203 (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:ibn:ijcjnl:v:10:y:2018:i:1:p:137-152

Access Statistics for this article

More articles in International Journal of Chemistry from Canadian Center of Science and Education Contact information at EDIRC.
Bibliographic data for series maintained by Canadian Center of Science and Education ().