Structure of native phosphoglucose isomerase from rabbit: conformational changes associated with catalytic function.
Phosphoglucose isomerase (PGI) is a housekeeping enzyme of metabolism that catalyses the interconversion of glucose 6-phosphate and fructose 6-phosphate, with roles in the glycolytic and gluconeogenic pathways. PGI is also a multifunctional protein that manifests the properties of a cytokine in a wide array of cellular processes, including the production of immunoglobulin by B cells and tumour-cell differentiation. The crystal structure of PGI in the native form from rabbit muscle has been solved at a resolution of 2.5 A by a combination of multiple isomorphous replacement and multi-crystal averaging techniques. Comparison with published structures of rabbit PGI in complex with three inhibitors and with the substrate fructose 6-phosphate reveals a number of conformational changes that may be associated with catalytic function. These occur in the small domain around the sugar phosphate-binding site, in a small helix carrying His388 and in a helix near the C-terminal end. One of these may be the structural rearrangement that has been postulated to be the rate-limiting step for catalysis.
Davies
Christopher
C
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA. davies@musc.edu
Muirhead
Hilary
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits
D008024:Ligands; D005956:Glucose-6-Phosphate Isomerase