Correlation Engine 2.0
Clear Search sequence regions

We demonstrate how tryptophanyl-tRNA synthetase uses conformation-dependent Mg(2+) activation to couple catalysis of tryptophan activation to specific, functional domain movements. Rate acceleration by Mg(2+) requires ∼-6.0 kcal/mol in protein⋅Mg(2+) interaction energy, none of which arises from the active site. A highly cooperative interaction between Mg(2+) and four residues from a remote, conserved motif that mediates the shear of domain movement (1) destabilizes the pretransition state conformation, thereby (2) inducing the Mg(2+) to stabilize the transition state for k(cat) by ∼-5.0 kcal/mol. Cooperative, long-range conformational effects on the metal therefore convert an inactive Mg(2+) coordination into one that can stabilize the transition state if, and only if, domain motion occurs. Transient, conformation-dependent Mg(2+) activation, analogous to the escapement in mechanical clocks, explains vectorial coupling. Copyright © 2012 Elsevier Ltd. All rights reserved.


Violetta Weinreb, Li Li, Charles W Carter. A master switch couples Mg²⁺-assisted catalysis to domain motion in B. stearothermophilus tryptophanyl-tRNA Synthetase. Structure (London, England : 1993). 2012 Jan 11;20(1):128-38

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 22244762

View Full Text