Architectural underpinnings of the genetic code for glutamine.

Biochemistry
Eleonora M Corigliano, John J Perona

Abstract

Structure-based mutational analysis was used to probe the architecture of the glutamine binding pocket in Escherichia coli glutaminyl-tRNA synthetase (GlnRS). Crystallographic studies of several different GlnRS complexes in a lattice that supports catalytic activity have shown that the glutamine amide group makes only ambiguous hydrogen-bonding interactions with a tyrosine hydroxyl and bound water molecule, rather than the highly specific hydrogen-bonding and electrostatic interactions made by the substrate amino acid in all other nonediting tRNA synthetases. Further, the amide oxygen of substrate glutamine accepts a hydrogen bond from the 3'-ribose hydroxyl group of ATP, an unusual distal substrate-substrate interaction also not observed in any other tRNA synthetase complex. Steady-state and pre-steady-state kinetic analysis using a 3'-dATP analogue in place of ATP shows that removal of this distal interaction does not affect K(m) for the analogue as compared with ATP, yet decreases the efficiency of aminoacylation by 10(3)-fold while significantly elevating K(m) for glutamine. In other experiments, mutation of eight nearly fully conserved residues in the glutamine binding pocket reveals decreases in k(cat)/K(m) ranging from 5...Continue Reading

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Citations

Oct 19, 2012·Biochemistry·John J Perona, Andrew Hadd
Sep 9, 2015·Journal of Molecular Biology·M J LajoieG M Church
Mar 15, 2011·Structure·Annia Rodríguez-Hernández, John J Perona
Sep 12, 2014·The Journal of Biological Chemistry·Charles W Carter
Oct 22, 2013·The Journal of Biological Chemistry·Li Li, Charles W Carter

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