Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps.
The second enzyme in the glycolytic pathway, phosphoglucose isomerase (PGI), catalyses an intracellular aldose-ketose isomerization. Here we describe the human recombinant PGI structure (hPGI) solved in the absence of active site ligands. Crystals isomorphous to those previously reported were used to collect a 94% complete data set to a limiting resolution of 2.1 A. From the comparison between the free active site hPGI structure and the available human and rabbit PGI (rPGI) structures, a mechanism for protein initial catalytic steps is proposed. Binding of the phosphate moiety of the substrate to two distinct elements of the active site is responsible for driving a series of structural changes resulting in the polarisation of the active site histidine, priming it for the initial ring-opening step of catalysis.
Cordeiro
A T
AT
Laboratory of Protein Crystallography and Structural Biology, Physics Institute of São Carlos, University of São Paulo-USP, Av Trabalhador Sãocarlense 400, PO Box 369, 13566-590 São Carlos-SP, Brazil.
Godoi
P H C
PH
Silva
C H T P
CH
Garratt
R C
RC
Oliva
G
G
Thiemann
O H
OH
D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D014961:X-Ray Diffraction
D005636:Fructosephosphates; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D005956:Glucose-6-Phosphate Isomerase