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Journal of Amino Acids
Volume 2013 (2013), Article ID 407616, 7 pages
http://dx.doi.org/10.1155/2013/407616
Research Article

Long-Lasting Effects of Oxy- and Sulfoanalogues of L-Arginine on Enzyme Actions

1Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
2Faculty of Mathematics and Natural Sciences, South-West University “Neofit Rilski”, 2700 Blagoevgrad, Bulgaria
3Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

Received 5 June 2013; Revised 20 August 2013; Accepted 15 September 2013

Academic Editor: Hieronim Jakubowski

Copyright © 2013 Tatyana A. Dzimbova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Arginine residues are very important for the structure of proteins and their action. Arginine is essential for many natural processes because it has unique ionizable group under physiological conditions. Numerous mimetics of arginine were synthesized and their biological effects were evaluated, but the mechanisms of actions are still unknown. The aim of this study is to see if oxy- and sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase (HArgS)—an enzyme responsible for coupling of L-arginine with its cognate tRNA in a two-step catalytic reaction. We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action. Three analogues of arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg), can be recognized as substrates of HArgS when incorporated in different peptide and protein sequences instead of L-arginine. Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action. All these observations could explain the long-lasting nature of the effects of the arginine analogues.