Nanometer propagation of millisecond motions in V-type allostery.
Imidazole glycerol phosphate synthase (IGPS) is a V-type allosteric enzyme, which is catalytically inactive for glutamine hydrolysis until the allosteric effector, N'-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide (PRFAR) binds 30 Å away. In the apo state, NMR relaxation dispersion experiments indicate the absence of millisecond (ms) timescale motions. Binding of the PRFAR to form the active ternary complex is endothermic with a large positive entropy change. In addition, there is a protein wide enhancement of conformational motions in the ternary complex, which connect the two active sites. NMR chemical shift changes and acrylamide quenching experiments suggest that little in the way of structural changes accompany these motions. The data indicate that enzyme activation in the ternary complex is primarily due to an enhancement of ms motions that allows formation of a population of enzymatically active conformers.
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
James M
JM
Lipchock
J Patrick
JP
Loria
D000495:Allosteric Site / Q000502:physiology*; D000619:Aminohydrolases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D019277:Entropy; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D008958:Models, Molecular; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D012265:Ribonucleotides / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
D007093:Imidazoles; D008024:Ligands; D012265:Ribonucleotides; C081348:N(1)-((5'-phosphoribulosyl)formimino)-5-aminoimidazo-4-carboxamide ribonucleotide; C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases