科研之友
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摘要
Aminoacylation reaction is a vital step of protein synthesis. The reaction takes place within the active site of aminoacyl tRNA synthetase (aaRS) and involves amino acid (AA) as well as adenosine triphosphate (ATP) as substrate. The twenty aaRSs are divided into two classes based on their primary structural sequence as well as three dimensional structures. Several differences in the structures and the reaction mechanism of the second step of aminoacylation reaction of two classes of aaRS are well known. However, no significant difference is reported in the mechanism of first step of aminoacylation reaction of class I and class II aaRSs to the best of our knowledge: The aim of the present work is to analyze the microscopic details of the structure of the reactant state and product (adenylate) state of the first step of aminoacylation reaction for class I and class II aaRSs and relate with the reaction mechanism of the activation step. The present study revealed a significant difference between class I (GluRS, GInRS, TyrRS, TrpRS, LeuRS, VaIRS, IleRS, CysRS, MetRS) and class II aaRSs (HisRS, LysRS, ProRS, AspRS, AsnRS, AlaRS, GlyRS, PheRS, ThrRS) based on the crystal structure. analysis and quantum mechanical analysis of electrostatic potential. We show for the first time that the modes of nucleophilic attack in the activation step in class I and class II aaRSs are significantly different. The syn oxygen atom of the carboxylic acid group of AA attacks in case of class I aaRSs while the anti oxygen atom perform the same job for class II aaRSs. The approach of syn oxygen atom is favorable for class I aaRS while for class II aaRSs the approach of anti oxygen is more favorable in reactant state. Quantum mechanical calculation of electrostatic potential explains the hitherto unknown microscopic differences in the reaction mechanism in the two cases.
- 出版日期2012-11
