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Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model

DOI: 10.1074/jbc.M109.079905 DOI Help
PMID: 20123988 PMID Help

Authors: Hugh Morgan (University of Edinburgh) , Iain Mcnae (University of Edinburgh) , Matthew Nowicki (University of Edinburgh) , Veronique Hannaert (Universite Catholique de Louvain) , Paul A. M. Michels (Universite┬┤ Catholique de Louvain) , Linda A. Fothergill-gilmore (University of Edinburgh) , Malcolm Walkinshaw (University of Edinburgh)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry , VOL 285 (17) , PAGES 12892 - 12898

State: Published (Approved)
Published: April 2010
Diamond Proposal Number(s): 1225

Abstract: Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognizable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase, from Leishmania mexicana. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6┬░ rigid body rocking motion of the A- and C-domain cores in each of the four subunits. However, formation of the R-state in this way is only part of the mechanism; eight essential salt bridge locks that form across the C-C interface provide tetramer rigidity with a coupled 7-fold increase in rate. The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control.

Journal Keywords: Animals; Leishmania; Models; Chemical; Models; Molecular; Protein; Tertiary; Protozoan; Pyruvate Kinase

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 27/09/2011 18:26

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