African Journal of
Pure and Applied Chemistry

  • Abbreviation: Afr. J. Pure Appl. Chem.
  • Language: English
  • ISSN: 1996-0840
  • DOI: 10.5897/AJPAC
  • Start Year: 2007
  • Published Articles: 368

Article in Press

Determination Of Interaction Sites Of Purine And Its Derivatives In Xanthine Oxidase Enzyme

Temesgen Nurlign Chekol

  •  Received: 04 June 2019
  •  Accepted: 02 August 2019
The role of Moco in xanthine oxidase enzyme 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 purpose of the study is to determine the interaction sites of different substrates in the binding pocket amino acid residues at molybdenum enzyme active site. The Mulliken atomic charges were compiled from the output files to characterize the interaction sites of the optimized structures. The molecular orbital analyses for the constituent chemical fragments were performed using AOMix software program to determine their percentage compositions. The variation in partial charges on the Molybdenum metal of the active site indicates that the tendency of the metal to accept the partial charges from the substrate carbon during interaction. This effect is due to the role of the binding pocket amino acid residues in activating the active site and providing the substrate proper orientation for the nucleophilic reaction to occur. More electrophile species are expected to undergo better nucleophilic reactions than those bearing less positive charges on their carbon atoms of the interaction sites. However, this may not be always true to determine the most favorable interaction sites of the unbound substrates based on their partial charges. This is the reason why the most favorable interaction site of purine is at its C6 position (its partial charge, qc = 0.009193), rather than the most electrophile interaction site at its C8 position (its partial charge, qc = 0.153024). Thus, it is better to consider the % compositions of carbon on its HOMO orbitals for purine and its derivatives to determine the most favorable interaction sites. Finally, we clearly show that % contribution for Cs-HOMO (for Pu-C6) is the highest (4.96) in comparing to the other two interaction sites of Pu-C2 (0.93) and Pu-C8 (3.68). Therefore, we can suggest that the most favorable interaction site during enzyme catalyzed reaction for purine is at C6.

Keywords: Binding pocket, Mulliken atomic charge, Xanthine oxidase, Substrate-enzyme complex, Hydrogen bonding.