Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates; comparison with phosphomannoisomerase

Malaisse‐Lagae, Francine; Liemans, Veronique; Yaylali, Beyhan; Sener, Abdullah; Malaisse, Willy

doi:10.1016/0167-4838(89)90262-8

Cited by 29 publications

(20 citation statements)

References 15 publications

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“…2c shows the structure and some of the presumed active-site residues for PMI. Experimental evidence supports a proton transfer mechanism by means of a cis ene-diol intermediate (35), rather than by a hydride shift as for xylose isomerase (36,37).…”

Section: Resultsmentioning

confidence: 86%

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THEMATICS: A simple computational predictor of enzyme function from structure

Ondrechen

Clifton

Ringe

2001

Proc. Natl. Acad. Sci. U.S.A.

215

203

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We show that theoretical microscopic titration curves (THEMATICS) can be used to identify active-site residues in proteins of known structure. Results are featured for three enzymes: triosephosphate isomerase (TIM), aldose reductase (AR), and phosphomannose isomerase (PMI). We note that TIM and AR have similar structures but catalyze different kinds of reactions, whereas TIM and PMI have different structures but catalyze similar reactions. Analysis of the theoretical microscopic titration curves for all of the ionizable residues of these proteins shows that a small fraction (3-7%) of the curves possess a flat region where the residue is partially protonated over a wide pH range. The preponderance of residues with such perturbed curves occur in the active site. Additional results are given in summary form to show the success of the method for proteins with a variety of different chemistries and structures.T here is a need to develop methods to predict protein function from structure; this need becomes particularly acute as novel protein folds are discovered for which there are no proteins of similar structure with known function. We show that theoretical microscopic titration curves (THEMATICS) can be used to identify active-site residues in enzymes of known structure. This information will prove to be important in the current challenging quest to predict protein function from sequence and structure.Knowledge of protein sequences and structures has burgeoned very recently as a result of genome sequencing (1) and structural genomics efforts. To translate such information into tangible benefits to humankind, the next step is to develop methods that enable one to predict and to establish function from structure. Techniques used to predict function from sequence or function from structure are in their infancy and rely either on analogies to related proteins of known function (2-8) or on computational searches for binding sites by docking (9) of selected sets of small molecules onto the structure. For instance, recent work has searched the Protein Data Bank (PDB; ref. 10; http:͞͞ www.rcsb.org͞pdb͞) for previously unrecognized cation-binding sites (11).However, there is as yet no reliable method to identify active sites of enzymes or other interaction sites of proteins in the absence of biochemical data, even when the structure is known. There is a wealth of biochemical data that demonstrates that active-site residues involved in specific kinds of chemistry possess predictable chemical properties that enable one to identify them as active-site residues. The most important of these properties is a perturbed pK a that can be determined experimentally by pH titrations of the activity of the enzyme. Herein we demonstrate that theoretical titration functions can identify active-site residues that are involved in Brønsted acid-base chemistry for a variety of proteins, thereby identifying the active site from the location of the residues.In an experimental titration curve, one typically plots pH as a function of the volume of...

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Section: Resultsmentioning

confidence: 86%

“…PMI. PMI (32)(33)(34)(35) catalyzes the reversible interconversion of mannose 6-phosphate and fructose 6-phosphate. PMI is a metaldependent enzyme containing one atom of zinc per protein molecule.…”

Section: Resultsmentioning

confidence: 99%

THEMATICS: A simple computational predictor of enzyme function from structure

Ondrechen

Clifton

Ringe

2001

Proc. Natl. Acad. Sci. U.S.A.

215

203

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“…Second, low values for the fraction- Table 1 because the intramolecular transfer of ~H at the occasion of a single passage of D-glucose 6-phosphate to D-fructose 6-phosphate in the PGI reaction, when conducted in 2H20, amounts to at least 96% [3]. Such a low efficiency of deuteration at the occasion of a single conversion of the aldohexose ester to D-fructose 6-phosphate is unlikely in the case of the PMI reaction, which entails a lower fractional intramolecular H transfer than the PGI reaction [2]. However, in the case of the PMI reaction, the extent of back-and-forth interconversion of D-fructose 6-phosphate, generated from exogenous D-glucose, and D-mannose 6-phosphate seems quite variable from one cell type to another [2].…”

Section: Deuteration Of the C~ Old-fructose 6-phosphate In The Pgi Anmentioning

confidence: 89%

“…Such a low efficiency of deuteration at the occasion of a single conversion of the aldohexose ester to D-fructose 6-phosphate is unlikely in the case of the PMI reaction, which entails a lower fractional intramolecular H transfer than the PGI reaction [2]. However, in the case of the PMI reaction, the extent of back-and-forth interconversion of D-fructose 6-phosphate, generated from exogenous D-glucose, and D-mannose 6-phosphate seems quite variable from one cell type to another [2]. It should also be stressed that, except when c~ = [3, it is not possible to ascribe specifically to PGI or PMI one of the two fractional deuteration factors.…”

Section: Deuteration Of the C~ Old-fructose 6-phosphate In The Pgi Anmentioning

confidence: 95%

“…First, the reactions catalyzed by PGI and by PMI, respectively, result in the generation of two distinct diastereomers of C 1-deuterated D-fructose 6-phosphate [2]. Hence, even extensive back-and-forth interconversions of the latter ester and the corresponding aldohexose ester in only one of these two reactions cannot lead to the production of a bisdeuterated ester.…”

Section: Deuteration Of the C~ Old-fructose 6-phosphate In The Pgi Anmentioning

confidence: 98%

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Mathematical modelling for the generation of L-[3-2H,3-13C]lactic acid isotopomers by erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of2H2O

Malaisse

Biesemans²

1994

Mol Cell Biochem

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The production of C3-trisdeuterated, bisdeuterated, monodeuterated or non-deuterated L-[3-13C]lactate by human erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of 2H2O can be assessed by 13C NMR spectroscopy. Such a deuteration may occur at the level of the reactions catalyzed by phosphoglucoisomerase, phosphomannoisomerase, pyruvate kinase and glutamate-pyruvate transaminase. In this report, a mathematical model is proposed for the analysis of experimental data. It allows to estimate the relative extent of deuteration at each step of D-glucose metabolism. This approach may thus provide novel information on the extent of back-and-forth interconversion of either hexose 6-phosphates in both the phosphoglucoisomerase and phosphomannoisomerase reactions or pyruvate and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase.

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Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5‐phospho‐d‐arabinonhydrazide

et al. 2018

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Type I phosphomannose isomerases (PMIs) are zinc-dependent monofunctional metalloenzymes catalysing the reversible isomerization of d-mannose 6-phosphate to d-fructose 6-phosphate. 5-Phospho-d-arabinonhydrazide (5PAHz), designed as an analogue of the enediolate high-energy intermediate, strongly inhibits PMI from Candida albicans (CaPMI). In this study, we report the 3D crystal structure of CaPMI complexed with 5PAHz at 1.85 Å resolution. The high-resolution structure suggests that Glu294 is the catalytic base that transfers a proton between the C1 and C2 carbon atoms of the substrate. Bidentate coordination of the inhibitor explains the stereochemistry of the isomerase activity, as well as the absence of both anomerase and C2-epimerase activities for Type I PMIs. A detailed mechanism of the reversible isomerization is proposed.

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Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates; comparison with phosphomannoisomerase

Cited by 29 publications

References 15 publications

THEMATICS: A simple computational predictor of enzyme function from structure

THEMATICS: A simple computational predictor of enzyme function from structure

Mathematical modelling for the generation of L-[3-2H,3-13C]lactic acid isotopomers by erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of2H2O

Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5‐phospho‐d‐arabinonhydrazide

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