Biochemistry & Physiology: Open Access
Open Access

The Role of [bm XOR]-Glu1261 in Activating HOeq Terminal in the Binding Stage of Catalysis in Xanthine Oxidase Enzyme

Chekol TN^*

Department of Chemistry, College of Natural and Computational Science, Wolkite University, PO. BOX, 07, Ethiopia

Received Date: Mar 18, 2019 / Accepted Date: Apr 22, 2019 / Published Date: May 10, 2019

Citation: Chekol TN (2019) The Role of [bm XOR]-Glu1261 in Activating HOeq Terminal in the Binding Stage of Catalysis in Xanthine Oxidase Enzyme. Biochem Physiol 8: 251.

Copyright: © 2019 Chekol TN. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

To read the full article Peer-reviewed Article PDF

All molybdo-enzymes except nitrogenase, xanthine oxidase possess structurally similar molybdenum cofactor (Moco) in which molybdenum metal is ligated by a dithiolene side chain to a pyranopterin ring. The pterin cofactor has been proposed to participate in assisting the transfer of electrons from or to the active site containing molybdenum metal. Generally, the role of Moco is to position Mo correctly within the active site, control the redox behavior of the enzymes, allow the enzyme to gain its biological activity, and participate with its pterin ring system in the electron transfer to or from the molybdenum atom. The geometry of the active site in the presence of substrate and binding pocket amino acid (Glu1261) was constructed using GaussView 3.0 software program. All geometry optimizations of the structures were carried out using Gaussian 03 W (version 6.0) program software package. The Mulliken atomic charges and the total energies were computed from the output files of the optimized structures. The percentage compositions of different molecular fragments were generated using AOMIX software package. Oxyanion is responsible for the nucleophilic attack of the deficient carbon atom other than the hydroxyl group itself (OH). Therefore, the most favorable pathway in the initial stage of catalysis is the reaction that occurs after the abstraction of the equatorial acidic proton of the active site. This is because Oxyanion cannot form the stable Structure when it forms a double bond with Molybdenum metal. The amino acid residue, Glu1261 is proposed to play an important role in promoting the nucleophilicity of the HOeq ligand of the active site. That is, Glu1261 is in a close proximity to the equatorial hydroxyl group, HOeq capable of abstracting hydrogen from HOeq which causes the equatorial oxygen develops a negative charge (Oxyanion) for the nucleophilic attack on the deficient substrate carbon. Therefore, we can conclude that the role of Glu1261 is enhancing the nucleophilicity of HOeq ligand as it acts as a Lewis base to accept a proton from the HOeq ligand as well as stabilizing the tetrahedral Michaelis-Menten type intermediate at the transition state.

Keywords