1PB3

Sites of binding and orientation in a four location model for protein stereospecificity.

Summary for 1PB3

• Entry DOI: 10.2210/pdb1pb3/pdb
• Related: 1P8F 1PB1
• Descriptor: Isocitrate dehydrogenase [NADP], SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: isocitrate dehydrogense, idh, stereospecificity, entantiomer, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 46277.97

Authors

Mesecar, A.D.,Koshland Jr., D.E. (deposition date: 2003-05-14, release date: 2003-06-17, Last modification date: 2024-02-14)

Primary citation

Mesecar, A.D.,Koshland Jr., D.E.
Sites of Binding and Orientation in a Four-Location Model for Protein Stereospecificity.
IUBMB Life, 49:457-466, 2000

PubMed Abstract: 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.

PubMed: 10902579
DOI: 10.1080/152165400410326

Experimental method

X-RAY DIFFRACTION (1.7 Å)