Selectivity and specificity of substrate binding in methionyl-tRNA synthetase

Protein Science : a Publication of the Protein Society
Deepshikha DattaWilliam A Goddard

Abstract

The accuracy of in vivo incorporation of amino acids during protein biosynthesis is controlled to a significant extent by aminoacyl-tRNA synthetases (aaRS). This paper describes the application of the HierDock computational method to study the molecular basis of amino acid binding to the Escherichia coli methionyl tRNA synthetase (MetRS). Starting with the protein structure from the MetRS cocrystal, the HierDock calculations predict the binding site of methionine in MetRS to a root mean square deviation in coordinates (CRMS) of 0.55 A for all the atoms, compared with the crystal structure. The MetRS conformation in the cocrystal structure shows good discrimination between cognate and the 19 noncognate amino acids. In addition, the calculated binding energies of a set of five methionine analogs show a good correlation (R(2) = 0.86) to the relative free energies of binding derived from the measured in vitro kinetic parameters, K(m) and k(cat). Starting with the crystal structure of MetRS without the methionine (apo-MetRS), the putative binding site of methionine was predicted. We demonstrate that even the apo-MetRS structure shows a preference for binding methionine compared with the 19 other natural amino acids. On comparing the...Continue Reading

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Citations

Aug 19, 2007·Journal of the American Chemical Society·Youyong LiAbdelazize Laoui
Mar 7, 2006·Protein Engineering, Design & Selection : PEDS·Christopher L McClendonWilliam A Goddard
Aug 31, 2007·Journal of Molecular Graphics & Modelling·Jiyoung HeoWilliam A Goddard
Oct 30, 2018·Journal of the American Chemical Society·Bhaskar BhushanBenjamin G Davis

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