Vanadate: A potent inhibitor of multifunctional glucose-6-phosphatase

Singh, Jasbir; Robert, C Nordlie; Jorgenson, Roger A.

doi:10.1016/0304-4165(81)90129-x

Cited by 100 publications

(54 citation statements)

References 20 publications

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“…However, we can not rule out that ancestral active VHPOs contain only a single helix bundle that have then diverged into two distinct forms, either by dimerization or by gene-duplication followed by gene-fusion. In any case, this evolutionary relationship between phosphatases and VHPOs has some functional consequences: since the phosphate and vanadate binding sites are sufficiently similar, it has been demonstrated that the apo-form of VCPO exhibits phosphatase activity [101], whereas the phosphatases are strongly inhibited by vanadate [102]. In several 3D structures, bound phosphate was located in VHPOs in a similar manner than the vanadate group, either in the native Ci-VCPO [92] or in the VBPO of Corallina species [93,94,103].…”

Section: Similarities Between Vanadium Haloperoxidases and Acid Phospmentioning

confidence: 99%

Vanadium haloperoxidases: From the discovery 30 years ago to X-ray crystallographic and V K-edge absorption spectroscopic studies

Leblanc

Vilter

Fournier

et al. 2015

Coordination Chemistry Reviews

128

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In the environment, vanadium-dependent haloperoxidases (VHPO) are likely to play a key role in the production of biogenic organo-halogens. These enzymes contain vanadate as a prosthetic group, and catalyze, in the presence of hydrogen peroxide, the oxidation of halide ions (Cl -, Br -or I -). They are classified according to the most electronegative halide that they can oxidize. Since the first discovery of a vanadium bromoperoxidase in the brown alga Ascophyllum nodosum thirty years ago, structural and mechanistic studies have been mainly conducted on two types of VHPO, chloro-and bromoperoxidases, and more recently on a vanadium-dependent iodoperoxidase. In this review, we highlight the main progress obtained on the structure-function relation of these proteins, based on biochemistry, crystallography and X-ray absorption spectroscopy (XAS). The comparison of 3D protein structures of the different VHPO helped identify the residues that govern the molecular mechanisms of catalysis and specificity of VHPO. Vanadium K-edge XAS gave further important insight to understand the fine changes around the vanadium cofactor during the catalytic cycle. The combination of different structural approaches, at different scales of resolution, shed new light on biological vanadium coordination in the active site, and its importance for the catalytic cycle and halide specificity of vanadium haloperoxidases. Keywords (max 6)Vanadium-dependent haloperoxidase, vanadium coordination, crystallographic structure, structural evolution, oligomeric state, X-ray absorption spectroscopy on biological vanadium

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Section: Similarities Between Vanadium Haloperoxidases and Acid Phospmentioning

confidence: 99%

Vanadium haloperoxidases: From the discovery 30 years ago to X-ray crystallographic and V K-edge absorption spectroscopic studies

Leblanc

Vilter

Fournier

et al. 2015

Coordination Chemistry Reviews

128

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“…As such, vanadate is also known to compete in enzymatic reaction involving orthophosphate, apparently by molecular and ionic mimicry (Clarkson, 1993). Furthermore, many enzymes that function via a phosphoenzyme intermediate, including some phosphatases (Singh et al, 1981), or that bind ATP or other high-energy phosphate compounds (Cantley et al, 1978;Karlish et al, 1979). are sensitive to vanadate.…”

Section: Dxh-(x25)-gdxxd-(x2s)-gnh(d/e) Sequence Is Foundmentioning

confidence: 99%

Identification of a novel phosphatase sequence motif

1997

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Abstract:We have identified a novel, conserved phosphatase sequence motif, KXXXXXXRP-(X12.54)-PSGH-(X31.54)-SRXXXXX HXXXD, that is shared among several lipid phosphatases, the mammalian glucose-6-phosphatases, and a collection of bacterial nonspecific acid phosphatases. This sequence was also found in the vanadium-containing chloroperoxidase of Curvularia inaequalis. Several lines of evidence support this phosphatase motif identification. Crystal structure data on chloroperoxidase revealed that all three domains are in close proximity and several of the conserved residues are involved in the binding of the cofactor, vanadate, a compound structurally similar to phosphate. Structurefunction analysis of the human glucose-6-phosphatase has shown that two of the conserved residues (the first domain arginine and the central domain histidine) are essential for enzyme activity. This conserved sequence motif was used to identify nine additional putative phosphatases from sequence databases, one of which has been determined to be a lipid phosphatase in yeast.Keywords: chloroperoxidase; homology; glucose-6-phosphatase; lipid phosphatase; motif; nonspecific acid phosphatase; phosphatase Phosphatases (phosphohydrolases) catalyze the hydrolysis of phosphoester and phosphoanhydride bonds of a diverse set of substrates including phosphorylated sugars, proteins, nucleic acids, and lipids (Boyer et al., 1961). Various criteria have been used to classify phosphatases into families. For example, phosphatases are classified on the basis of characteristics such as the molecular nature of the phosphate-containing substrate (phosphomonoester or phosphodiester), substrate type (proteinaceous or non-proteinaceous), substrate specificity (glucose-6-phosphatases, protein-tyrosine phosphatases), pH optimum (acid and alkaline phosphatases), size (high and low molecular weight phosphatases), and on the identity of the enzyme residue that is transiently phosphorylated during catalysis (histidine, serine, and cysteine phosphatases) (Boyer et al

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“…To prove this hypothesis, intravesicular glucose-6-phosphate and glucose contents were determined when glucose-6-phosphatase was inactivated by a mild acidic pretreatment of microsomes (16,37), or inhibited by the competitive inhibitor vanadate (46). At low glucose-6-phosphate concentration (0.2 mM), these treatments slightly influenced the intravesicular glucose-6-phosphate levels (data not shown).…”

Section: Table I Intravesicular Glucose and Glucose-6-phosphate Contementioning

confidence: 99%

Demonstration of a Metabolically Active Glucose-6-phosphate Pool in the Lumen of Liver Microsomal Vesicles

Bánhegyi

Marcolongo

Fulceri

et al. 1997

Journal of Biological Chemistry

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Glucose-6-phosphate transport was investigated in rat or human liver microsomal vesicles using rapid filtration and light-scattering methods. Upon addition of glucose-6-phosphate, rat liver microsomes accumulated the radioactive tracer, reaching a steady-state level of uptake. In this phase, the majority of the accumulated tracer was glucose, but a significant intraluminal glucose-6-phosphate pool could also be observed. The extent of the intravesicular glucose pool was proportional with glucose-6-phosphatase activity. The relative size of the intravesicular glucose-6-phosphate pool (irrespective of the concentration of the extravesicular concentration of added glucose-6-phosphate) expressed as the apparent intravesicular space of the hexose phosphate was inversely dependent on glucose-6-phosphatase activity. The increase of hydrolysis by elevating the extravesicular glucose-6-phosphate concentration or temperature resulted in lower apparent intravesicular glucose-6-phosphate spaces and, thus, in a higher transmembrane gradient of glucose-6-phosphate concentrations. In contrast, inhibition of glucose-6-phosphate hydrolysis by vanadate, inactivation of glucose-6-phosphatase by acidic pH, or genetically determined low or absent glucose-6-phosphatase activity in human hepatic microsomes of patients suffering from glycogen storage disease type 1a led to relatively high intravesicular glucose-6-phosphate levels. Glucose-6-phosphate transport investigated by light-scattering technique resulted in similar traces in control and vanadate-treated rat microsomes as well as in microsomes from human patients with glycogen storage disease type 1a. It is concluded that liver microsomes take up glucose-6-phosphate, constituting a pool directly accessible to intraluminal glucose-6-phosphatase activity. In addition, normal glucose-6-phosphate uptake can take place in the absence of the glucose-6-phosphatase enzyme protein, confirming the existence of separate transport proteins.

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Vanadate: A potent inhibitor of multifunctional glucose-6-phosphatase

Cited by 100 publications

References 20 publications

Vanadium haloperoxidases: From the discovery 30 years ago to X-ray crystallographic and V K-edge absorption spectroscopic studies

Vanadium haloperoxidases: From the discovery 30 years ago to X-ray crystallographic and V K-edge absorption spectroscopic studies

Identification of a novel phosphatase sequence motif

Demonstration of a Metabolically Active Glucose-6-phosphate Pool in the Lumen of Liver Microsomal Vesicles

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