Role of coupled dynamics in the catalytic activity of prokaryotic-like prolyl-tRNA synthetases.

Biochemistry
Brianne L SanfordSanchita Hati

Abstract

Prolyl-tRNA synthetases (ProRSs) have been shown to activate both cognate and some noncognate amino acids and attach them to specific tRNA(Pro) substrates. For example, alanine, which is smaller than cognate proline, is misactivated by Escherichia coli ProRS. Mischarged Ala-tRNA(Pro) is hydrolyzed by an editing domain (INS) that is distinct from the activation domain. It was previously shown that deletion of the INS greatly reduced cognate proline activation efficiency. In this study, experimental and computational approaches were used to test the hypothesis that deletion of the INS alters the internal protein dynamics leading to reduced catalytic function. Kinetic studies with two ProRS variants, G217A and E218A, revealed decreased amino acid activation efficiency. Molecular dynamics studies showed motional coupling between the INS and protein segments containing the catalytically important proline-binding loop (PBL, residues 199-206). In particular, the complete deletion of INS, as well as mutation of G217 or E218 to alanine, exhibited significant effects on the motion of the PBL. The presence of coupled dynamics between neighboring protein segments was also observed through in silico mutations and essential dynamics analysis...Continue Reading

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Citations

Jul 18, 2015·International Journal of Molecular Sciences·Rongzhong LiSamuel S Cho
Jan 24, 2016·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Sanchita Hati, Sudeep Bhattacharyya
Mar 5, 2014·The Protein Journal·Nicholas WarrenSanchita Hati
Sep 23, 2019·Biophysical Journal·Lauren M AdamsSudeep Bhattacharyya
Mar 21, 2015·The Journal of Physical Chemistry. B·Saheb Dutta, Nilashis Nandi
Jul 24, 2021·ACS Catalysis·Quin H HuSudeep Bhattacharyya

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