The intrinsic dynamics of enzymes are known to be critical for catalytic functions. However, there are still limited information available regarding how dynamics favor enzymes to achieve their enormous rate enhancement. To better understand the molecular mechanism of the interplay between dynamics and catalysis, we are studying an important family of enzymes - aminoacyl-tRNA synthetases. These enzymes catalyze the covalent attachment of amino acids to their cognate tRNA. This reaction is known as aminoacylation of tRNA and is crucial for protein synthesis in all living organisms. These essential enzymes are large proteins, comprised of multiple domains. To explore if dynamics play a direct role in catalysis by favoring bond breaking/formation or an indirect role by modulating substrate recognition/binding, we modeled the prolyl-adenylate formation. This reaction is catalyzed by prolyl-tRNA synthetase, a member of aminoacyl-tRNA synthetases family. We have used quantum mechanical/molecular mechanical (QM/MM) approaches to model and compute energetics of the adenylate formation reaction in enzyme and enzyme-free (aqueous) system. We also explored the substrate binding using molecular dynamics simulations. Herein, the preliminary results, which will include the binding free energy and the free-energy of activation of prolyl-adenylate formation by the wild type and mutant enzymes will be presented.

Role of intrinsic dynamics on substrate binding and catalysis of <i>Escherichia coli </i>prolyl-tRNA synthetase

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Role of intrinsic dynamics on substrate binding and catalysis of Escherichia coli prolyl-tRNA synthetase