Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrine motility factor, and differentiation mediator.
The multifunctional protein phosphoglucose isomerase, also known as neuroleukin, autocrine motility factor, and differentiation and maturation mediator, has different roles inside and outside the cell. In the cytoplasm, it catalyzes the second step in glycolysis. Outside the cell, it serves as a nerve growth factor and cytokine. We have determined the three-dimensional structure of rabbit muscle phosphoglucose isomerase complexed with the competitive inhibitor D-gluconate 6-phosphate by X-ray crystallography at 2.5 A resolution. The structure shows that the enzyme is a dimer with two alpha/beta-sandwich domains in each subunit. The location of the bound D-gluconate 6-phosphate inhibitor leads to the identification of residues involved in substrate specificity (Ser209, Ser159, Thr214, Thr217, and Thr211). The results of previously published kinetic studies suggest that a lysine and a histidine are involved in the catalytic mechanism. The crystal structure suggests active site residues Lys518 and His388 might be these residues. In addition, the positions of amino acid residues that are substituted in the genetic disease nonspherocytic hemolytic anemia suggest how these substitutions can result in altered catalysis or protein stability.
Jeffery
C J
CJ
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Bahnson
B J
BJ
Chien
W
W
Ringe
D
D
Petsko
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000502:physiology; D018360:Crystallography, X-Ray; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006019:Glycolysis; D006133:Growth Substances / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D017510:Protein Folding; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013552:Swine
D006133:Growth Substances; D005956:Glucose-6-Phosphate Isomerase