The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme

Temesgen Nurlign Chekol

doi:doi:10.11648/j.ajcbe.20180202.12

| Peer-Reviewed |

The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme

Temesgen Nurlign Chekol

Received: 26 October 2018 Accepted: 3 December 2018 Published: 3 January 2019

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Xanthine oxidase is one of the most useful molybdenum containing enzymes, which catalyzes a wide range of purine derivative heterocyclic substrates. In order for the interaction between the reactants to take place, the substrates are expected to enter the binding pocket and attain a proper orientation with the help of binding pocket amino acid residues. Therefore, the study is mainly focused to understand the role of binding pocket amino acid residues in providing the substrates proper orientation for the nucleophilic reaction to take place. The binding pocket amino acids residues in particular, Glu₈₀₂ and Arg₈₈₀ were proposed to create a hydrogen bonding microenvironment and modulate the near attack conformation (NAC) in the presence of substrates. In order to probe the behavior of the substrates, inside the binding pocket, the electronic structure calculations were performed. Moreover, the activation of the active site was proposed to take place after the acidic proton is abstracted from the HOeq by [bmXOR]-Glu₁₂₆₁. The Oxyanion of the active site is responsible for the nucleophilic attack on the deficient carbon center of the given substrates. In general, the purpose of the study is to relate the roles of amino acid residues in the reactivities of enzyme catalyzed reactions and to determine the most favorable path way during the activation of the active site by Glu₁₂₆₁.

DOI	10.11648/j.ajcbe.20180202.12
Published in	American Journal of Chemical and Biochemical Engineering (Volume 2, Issue 2, December 2018)
Page(s)	27-49
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Xanthine Oxidase, Amino Acid Residues, Proper Orientation, Active Site, Substrate, Catalysis

References

[1]	Hille, R., (1996). The Mononuclear Molybdenum Enzymes. Chem. Rev., 96, 2757 - 2816.
[2]	Voityuk, A. A., Albert, K., Roman, J. M., Huber. R., and Rosch. N., (1997). Substrate Oxidation in the Active Site of Xanthine Oxidase and Related Enzymes. A Model Density Functional Study. Inorg. Chem., 37, 176 - 180.
[3]	Bayse, A. C., (2009). Density-functional theory models of xanthine oxidoreductase activity: comparison of substrate tautomerization and protonation. J. Chem.soc., 29, 2306 - 2314.
[4]	Pauff, J. M., Cao. H, and Hille. R., (2009). Substrate Orientation and Catalysis at the Molybdenum Site in Xanthine Oxidase. J. Biol. Chem., 284, 8760 – 8767.
[5]	Garattini, E., Menedel, R., Romao, M. J., Wright, R., and Terao, M., (2003). Mammalian molybdo–flavoenzymes, an expanding family of proteins: Structure, genetics, regulation, function and pathophysiology. Biochem. J., 372, 15 - 32.
[6]	Hernandez, B., Luque, J. F., and Orozco, M., (1996). Tautomerism of Xanthine Oxidase Substrates Hypoxanthine and Allopurinol. J. Org. Chem., 61, 5964 - 5971.
[7]	Greenlee, L., and Handle. P., (1964). Xanthine Oxidase: Influence of pH on substrate specificity. J. Biol. Chem., 239, 1090 - 1095.
[8]	Amano, T., Ochi, N., Sato, H., and Sakaki, S., (2007). Oxidation Reaction by Xanthine Oxidase. Theoretical Study of Reaction Mechanism. J. Am. Chem. Soc., 129, 8131 - 8138.
[9]	Zhang, H. X., and Wu, D., (2005). A Theoretical Study on the Mechanism of the Reductive Half-Reaction of Xanthine Oxidase. Inorg. Chem., 44, 1466 - 1471.
[10]	Bayse, A. C., (2005). Theoretical Characterization of the “Very Rapid” Mo (V) Species Generated in the Oxidation of Xanthine Oxidase. Inorg. Chem., 45, 2199 - 2202.
[11]	Enroth, C., Eger, T. B., Okamoto, K., Nishino, T., Nishino, T., and Emil F., Pai, E. F., (2000). Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion. J. Biol. Chem., 97, 10723-10728.
[12]	Yamaguchi, Y., Matsumura, T., Ichida, K., Okamoto, K, and Takeshi Nishino, T., (2007). Human Xanthine Oxidase Changes its Substrate Specificity to Aldehyde Oxidase Type upon Mutation of Amino Acid Residues in the Active Site: Roles of Active Site Residues in Binding and Activation of Purine Substrate. J. Biol. Chem., 141, 513 – 524.
[13]	Martz, E., (2002). Protein Explorer: Easy Yet Powerful Macromolecular Visualization, Trends in Biochem. Sci., 27 (February): 107 - 109. http://proteinexplorer.org).
[14]	Pauff, J. M., Cao, H., and Hille, R., (2010). Substrate orientation and catalytic specificity in the action of xanthine oxidase: The sequential hydroxylation of hypoxanthine to uric acid. J. Biol. Chem., 284, 8760 - 8767.
[15]	Pauff, J. M., Zhang, J., Bell, C. E, and Hille, R., (2008). Substrate Orientation in Xanthine Oxidase. J. Biol. Chem,. 283, 4818 – 4824.
[16]	Pauff, J. M., Hemann, C. F., Hemann, N. J., Leimkuhler, S., and Hille, R., (2007). The Role of Argenine 310 in Catalysis and Substrate Specificity in Xanthine Dehydrogenase from Rhodobacter capsulatus. J. Biol. Chem., 282, 12785 – 12790.
[17]	Dinesh, S., Shikha, G. W., Bhavana, G. W., Nidi, S., and Dileep, S., (2012). Biological activities of purine analoges. Rev. J. Pharm. and Sci. Innov.., 1 (2), 29 - 34.
[18]	Romao, M. J., (2009). Molybdenum and tungsten enzymes: a crystallographic and mechanistic Overview. J. Royal. Soc. 17, 4053 - 4068.
[19]	Hille, R., (2006). Structure and Function of Xanthine Oxidoreductase. Eur. J. Inorg. Chem., 36, 1913 - 1926.
[20]	Pauff, J. M., Cao. H, and Hille, R., (2010). Substrate Orientation and the origin catalytic power in Xanthine oxidoreductase. In. J. Chem., 50, 355 - 362.
[21]	Hille, R, and Nishino, T., (1995). Xanthine oxidase and xanthine dehydrogenase. J. Bio Chem., 9, 995 - 1003.
[22]	Voityuk, A. A., Albert, K., Stlmeier, S. K., Nasluzov, V. A., Neyman, K. M., Hof, P., Huber. R., Romao, J. M, and Rosch. N., (1997). Prediction of Alternative Structures of the Molybdenum Site in the Xanthine Oxidase-Related Aldehyde Oxido Reductase. J. Am. Chem. Soc., 119, 3159 - 3160.
[23]	Leimkuhler, S. Stockert, A. L., Igarashi, K., Nishino, T., and Hille, R., (2004). The Role of Active Site Glutamate Residues in Catalysis of Rhodobacter capsulatus Xanthine Dehydrogenase. J. Biol. Chem., 279, 40437 - 40444.
[24]	Matsumoto, K., Okamoto, K., Hille, R., Eger, B. T., Pai, E. F., and Nishino, T., (2004). The crystal structure of XOR during catalysis: Implications for reaction mechanism and enzyme inhibition. Proc. Nat. Acad. Sci. 101, 7931 - 7936.
[25]	Pauff, J. M., Zhang, J., Bell, C. E, and Hille, R., (2007). Substrate Orientation in Xanthine Oxidase crystal structure with HMP. J. Biol. Chem., 6, 1 - 16.
[26]	Becke, A. D. J., (1993). Density Functional Thermo chemistry 3: the Role of Exact Exchange. J. Chem. Phys., 98, 5648 - 5652.
[27]	Lee, C., Yang, W., and Parr, R. G., (1988). Development of the Colle-Salvetti conelation energy formula into a functional of the electron density. J. Phys. Rev., 37, 785 - 789.

Cite This Article

Plain Text BibTeX RIS

APA Style

Temesgen Nurlign Chekol. (2019). The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. American Journal of Chemical and Biochemical Engineering, 2(2), 27-49. https://doi.org/10.11648/j.ajcbe.20180202.12

Copy | Download

ACS Style

Temesgen Nurlign Chekol. The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. Am. J. Chem. Biochem. Eng. 2019, 2(2), 27-49. doi: 10.11648/j.ajcbe.20180202.12

Copy | Download

AMA Style

Temesgen Nurlign Chekol. The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. Am J Chem Biochem Eng. 2019;2(2):27-49. doi: 10.11648/j.ajcbe.20180202.12

Copy | Download

@article{10.11648/j.ajcbe.20180202.12,
  author = {Temesgen Nurlign Chekol},
  title = {The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme},
  journal = {American Journal of Chemical and Biochemical Engineering},
  volume = {2},
  number = {2},
  pages = {27-49},
  doi = {10.11648/j.ajcbe.20180202.12},
  url = {https://doi.org/10.11648/j.ajcbe.20180202.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcbe.20180202.12},
  abstract = {Xanthine oxidase is one of the most useful molybdenum containing enzymes, which catalyzes a wide range of purine derivative heterocyclic substrates. In order for the interaction between the reactants to take place, the substrates are expected to enter the binding pocket and attain a proper orientation with the help of binding pocket amino acid residues. Therefore, the study is mainly focused to understand the role of binding pocket amino acid residues in providing the substrates proper orientation for the nucleophilic reaction to take place. The binding pocket amino acids residues in particular, Glu802 and Arg880 were proposed to create a hydrogen bonding microenvironment and modulate the near attack conformation (NAC) in the presence of substrates. In order to probe the behavior of the substrates, inside the binding pocket, the electronic structure calculations were performed. Moreover, the activation of the active site was proposed to take place after the acidic proton is abstracted from the HOeq by [bmXOR]-Glu1261. The Oxyanion of the active site is responsible for the nucleophilic attack on the deficient carbon center of the given substrates. In general, the purpose of the study is to relate the roles of amino acid residues in the reactivities of enzyme catalyzed reactions and to determine the most favorable path way during the activation of the active site by Glu1261.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme
AU  - Temesgen Nurlign Chekol
Y1  - 2019/01/03
PY  - 2019
N1  - https://doi.org/10.11648/j.ajcbe.20180202.12
DO  - 10.11648/j.ajcbe.20180202.12
T2  - American Journal of Chemical and Biochemical Engineering
JF  - American Journal of Chemical and Biochemical Engineering
JO  - American Journal of Chemical and Biochemical Engineering
SP  - 27
EP  - 49
PB  - Science Publishing Group
SN  - 2639-9989
UR  - https://doi.org/10.11648/j.ajcbe.20180202.12
AB  - Xanthine oxidase is one of the most useful molybdenum containing enzymes, which catalyzes a wide range of purine derivative heterocyclic substrates. In order for the interaction between the reactants to take place, the substrates are expected to enter the binding pocket and attain a proper orientation with the help of binding pocket amino acid residues. Therefore, the study is mainly focused to understand the role of binding pocket amino acid residues in providing the substrates proper orientation for the nucleophilic reaction to take place. The binding pocket amino acids residues in particular, Glu802 and Arg880 were proposed to create a hydrogen bonding microenvironment and modulate the near attack conformation (NAC) in the presence of substrates. In order to probe the behavior of the substrates, inside the binding pocket, the electronic structure calculations were performed. Moreover, the activation of the active site was proposed to take place after the acidic proton is abstracted from the HOeq by [bmXOR]-Glu1261. The Oxyanion of the active site is responsible for the nucleophilic attack on the deficient carbon center of the given substrates. In general, the purpose of the study is to relate the roles of amino acid residues in the reactivities of enzyme catalyzed reactions and to determine the most favorable path way during the activation of the active site by Glu1261.
VL  - 2
IS  - 2
ER  -

Copy | Download

Author Information

Temesgen Nurlign Chekol

Department of Chemistry, College of Natural and Computational Science, Wolikite University, Wolikite, Ethiopia

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Temesgen Nurlign Chekol. (2019). The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. American Journal of Chemical and Biochemical Engineering, 2(2), 27-49. https://doi.org/10.11648/j.ajcbe.20180202.12

Copy | Download

ACS Style

Temesgen Nurlign Chekol. The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. Am. J. Chem. Biochem. Eng. 2019, 2(2), 27-49. doi: 10.11648/j.ajcbe.20180202.12

Copy | Download

AMA Style

Temesgen Nurlign Chekol. The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme. Am J Chem Biochem Eng. 2019;2(2):27-49. doi: 10.11648/j.ajcbe.20180202.12

Copy | Download

@article{10.11648/j.ajcbe.20180202.12,
  author = {Temesgen Nurlign Chekol},
  title = {The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme},
  journal = {American Journal of Chemical and Biochemical Engineering},
  volume = {2},
  number = {2},
  pages = {27-49},
  doi = {10.11648/j.ajcbe.20180202.12},
  url = {https://doi.org/10.11648/j.ajcbe.20180202.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcbe.20180202.12},
  abstract = {Xanthine oxidase is one of the most useful molybdenum containing enzymes, which catalyzes a wide range of purine derivative heterocyclic substrates. In order for the interaction between the reactants to take place, the substrates are expected to enter the binding pocket and attain a proper orientation with the help of binding pocket amino acid residues. Therefore, the study is mainly focused to understand the role of binding pocket amino acid residues in providing the substrates proper orientation for the nucleophilic reaction to take place. The binding pocket amino acids residues in particular, Glu802 and Arg880 were proposed to create a hydrogen bonding microenvironment and modulate the near attack conformation (NAC) in the presence of substrates. In order to probe the behavior of the substrates, inside the binding pocket, the electronic structure calculations were performed. Moreover, the activation of the active site was proposed to take place after the acidic proton is abstracted from the HOeq by [bmXOR]-Glu1261. The Oxyanion of the active site is responsible for the nucleophilic attack on the deficient carbon center of the given substrates. In general, the purpose of the study is to relate the roles of amino acid residues in the reactivities of enzyme catalyzed reactions and to determine the most favorable path way during the activation of the active site by Glu1261.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - The Role of Binding Pocket Amino Acid Residues in Substrate Specificity Towards Xanthine Oxidase Enzyme
AU  - Temesgen Nurlign Chekol
Y1  - 2019/01/03
PY  - 2019
N1  - https://doi.org/10.11648/j.ajcbe.20180202.12
DO  - 10.11648/j.ajcbe.20180202.12
T2  - American Journal of Chemical and Biochemical Engineering
JF  - American Journal of Chemical and Biochemical Engineering
JO  - American Journal of Chemical and Biochemical Engineering
SP  - 27
EP  - 49
PB  - Science Publishing Group
SN  - 2639-9989
UR  - https://doi.org/10.11648/j.ajcbe.20180202.12
AB  - Xanthine oxidase is one of the most useful molybdenum containing enzymes, which catalyzes a wide range of purine derivative heterocyclic substrates. In order for the interaction between the reactants to take place, the substrates are expected to enter the binding pocket and attain a proper orientation with the help of binding pocket amino acid residues. Therefore, the study is mainly focused to understand the role of binding pocket amino acid residues in providing the substrates proper orientation for the nucleophilic reaction to take place. The binding pocket amino acids residues in particular, Glu802 and Arg880 were proposed to create a hydrogen bonding microenvironment and modulate the near attack conformation (NAC) in the presence of substrates. In order to probe the behavior of the substrates, inside the binding pocket, the electronic structure calculations were performed. Moreover, the activation of the active site was proposed to take place after the acidic proton is abstracted from the HOeq by [bmXOR]-Glu1261. The Oxyanion of the active site is responsible for the nucleophilic attack on the deficient carbon center of the given substrates. In general, the purpose of the study is to relate the roles of amino acid residues in the reactivities of enzyme catalyzed reactions and to determine the most favorable path way during the activation of the active site by Glu1261.
VL  - 2
IS  - 2
ER  -

Copy | Download