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A variant of rabbit phosphoglucose isomerase.

ABSTRACT: An autosomally inherited variant of the rabbit enzyme phosphoglucose isomerase that differs both electrophoretically and kinetically from the usual (wild-type) rabbit enzyme has been investigated. Animals homozygous for this character have an isomerase with considerably decreased activity (in the erythrocytes), an increased K(m) for fructose 6-phosphate, an increased K(i) for 6-phosphogluconate and a decreased stability towards heat and urea. The variant enzyme has been demonstrated in erythrocytes, leucocytes and tissues from the affected rabbits. The kinetic evidence suggests that the mutation present in the variant enzyme affects a histidine residue.

SUBMITTER: Welch SG

PROVIDER: S-EPMC1178956 | biostudies-other | 1970 Apr

REPOSITORIES: biostudies-other

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The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid.

Project description:Phosphoglucose isomerase (EC ) catalyzes the second step in glycolysis, the reversible isomerization of D-glucose 6-phosphate to D-fructose 6-phosphate. The reaction mechanism involves acid-base catalysis with proton transfer and proceeds through a cis-enediol(ate) intermediate. 5-Phospho-D-arabinonohydroxamic acid (5PAH) is a synthetic small molecule that resembles the reaction intermediate, differing only in that it has a nitrogen atom in place of C1. Hence, 5PAH is the best inhibitor of the isomerization reaction reported to date with a K(i) of 2 x 10(-7) M. Here we report the crystal structure of rabbit phosphoglucose isomerase complexed with 5PAH at 1.9 A resolution. The interaction of 5PAH with amino acid residues in the enzyme active site supports a model of the catalytic mechanism in which Glu-357 transfers a proton between C1 and C2 and Arg-272 helps stabilize the intermediate. It also suggests a mechanism for proton transfer between O1 and O2.

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Structural studies of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv.

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Glucose 6-Phosphate Accumulates via Phosphoglucose Isomerase Inhibition in Heart Muscle.

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Project description:Crystallization and preliminary crystallographic analysis of the phosphoglucose isomerase from a Bacillus subtilis native strain were carried out. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 145.7, b = 136.0, c = 109.1 A, beta = 119.4 degrees . The diffraction quality of the crystal was significantly improved from 2.4 A to greater than 1.9 A resolution by using the in situ flash-annealing method. A 98% complete data set with an overall R(merge) of 4.6% was collected using an R-AXIS IV(++) image-plate system and a copper rotating-anode X-ray generator. The crystals contained four molecules per asymmetric unit and the predicted solvent content and the Matthews coefficient (V(M)) were 46.8% and 2.3 A(3) Da(-1), respectively. Structure determination by the molecular-replacement method provided a reasonable solution for model building.

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Requirement for phosphoglucose isomerase of Xanthomonas campestris in pathogenesis of citrus canker.

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Crystallization and preliminary X-ray crystallographic study of phosphoglucose isomerase from Plasmodium falciparum.

Project description:Phosphoglucose isomerase (PGI) is a key enzyme in glycolysis and glycogenesis that catalyses the interconversion of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P). For crystallographic studies, PGI from the human malaria parasite Plasmodium falciparum (PfPGI) was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. X-ray diffraction data to 1.5 A resolution were collected from an orthorhombic crystal form belonging to space group P2(1)2(1)2(1) with unit-cell parameters a = 103.3, b = 104.1, c = 114.6 A. Structural analysis by molecular replacement is in progress.

| S-EPMC2833051 | biostudies-literature

Crystallization and preliminary X-ray characterization of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv.

Project description:Phosphoglucose isomerase is a ubiquitous enzyme that catalyzes the isomerization of D-glucopyranose-6-phosphate to D-fructofuranose-6-phosphate. The present investigation reports the expression, purification, crystallization and preliminary crystallographic studies of the phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv, which shares 46% sequence identity with that of its human host. The recombinant protein, which was prepared using an Escherichia coli expression system, was crystallized by the hanging-drop vapour-diffusion method. The crystals diffracted to a resolution of 2.8 A and belonged to the orthorhombic space group I2(1)2(1)2(1), with unit-cell parameters a = 109.0, b = 119.8, c = 138.9 A.

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Distant Non-Obvious Mutations Influence the Activity of a Hyperthermophilic Pyrococcusfuriosus Phosphoglucose Isomerase.

Project description:The cupin-type phosphoglucose isomerase (PfPGI) from the hyperthermophilic archaeon Pyrococcus furiosus catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. We investigated PfPGI using protein-engineering bioinformatics tools to select functionally-important residues based on correlated mutation analyses. A pair of amino acids in the periphery of PfPGI was found to be the dominant co-evolving mutation. The position of these selected residues was found to be non-obvious to conventional protein engineering methods. We designed a small smart library of variants by substituting the co-evolved pair and screened their biochemical activity, which revealed their functional relevance. Four mutants were further selected from the library for purification, measurement of their specific activity, crystal structure determination, and metal cofactor coordination analysis. Though the mutant structures and metal cofactor coordination were strikingly similar, variations in their activity correlated with their fine-tuned dynamics and solvent access regulation. Alternative, small smart libraries for enzyme optimization are suggested by our approach, which is able to identify non-obvious yet beneficial mutations.

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