1pb3
Sites of binding and orientation in a four location model for protein stereospecificity.
|
OverviewOverview
The stereospecificity of the enzyme isocitrate dehydrogenase was examined by steady-state kinetics and x-ray crystallography. The enzyme has the intriguing property that the apoenzyme in the absence of divalent metal showed a selectivity for the inactive l-enantiomer of the substrate isocitrate, whereas the enzyme containing magnesium showed selectivity for the physiologically active d-enantiomer. The hydrogen atom on the C2 carbon that is transferred during the reaction was, in both the d- and l-isocitrate complexes, in an orientation very close to that expected for delivery of a hydride ion to the cosubstrate NADP+. The beta-carboxylate that is eliminated as a CO2 molecule during the reaction occupied the same site on the protein in both the d- and l-isocitrate complexes. In addition, the C3 carbon was in the same protein site in both the d- and l-enantiomers. Only the fourth group, the OH atom, was in a very different position in the apo enzyme and in the metal-containing complexes. A four-location model is necessary to explain the enantiomeric specificity of IDH in contrast to the conventional three-point attachment model. The thermodynamic and kinetic ramifications of this model are explored.
About this StructureAbout this Structure
1PB3 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.
ReferenceReference
Sites of binding and orientation in a four-location model for protein stereospecificity., Mesecar AD, Koshland DE Jr, IUBMB Life. 2000 May;49(5):457-66. PMID:10902579
Page seeded by OCA on Thu Feb 21 14:26:58 2008