The Structure and Mechanism of myo-Inositol-1-Phosphate Synthase

Geiger, James H.; Jin, Xiangshu

doi:10.1007/0-387-27600-9_7

Cited by 27 publications

(54 citation statements)

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“…Phosphorylation of Ser-374 may perturb access of the substrate to the catalytic domain or may destabilize the induced fit by creating steric hindrance, thus decreasing catalytic activity. Additionally, the catalytic domain is populated with hydrophobic residues (15,17). The negative charge of the phosphate group may alter the electrostatic balance of these residues and thus cause further perturbation of enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

“…The crystal structure of yeast MIPS shows that it is a homotetramer ( Fig. 1B) (15,16), whereas mammalian MIPS exists as a trimer (10). Each monomer has three major domains: a catalytic domain that binds the substrate glucose 6-phosphate, an NAD ϩ -binding domain, and a central domain, consisting of the N and C termini, which stabilizes the two other domains (17).…”

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confidence: 99%

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Phosphorylation Regulates myo-Inositol-3-phosphate Synthase

Deranieh¹,

He²,

Caruso

et al. 2013

Journal of Biological Chemistry

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Background: myo-Inositol-3-phosphate synthase (MIPS) catalyzes the first step in de novo biosynthesis of inositol in eukaryotes. Results: MIPS is a phosphoprotein. Phosphorylation regulates the activity of yeast and human MIPS. Conclusion: Phosphorylation of MIPS is a novel regulatory mechanism of inositol biosynthesis. Significance: This may explain the causes and consequences of perturbation of inositol metabolism implicated in human disorders.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Phosphorylation Regulates myo-Inositol-3-phosphate Synthase

Deranieh¹,

He²,

Caruso

et al. 2013

Journal of Biological Chemistry

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“…Ins biosynthesis involves two enzymes: (1) D(L)- myo -inositol-3(1)-phosphate synthase (MIPS, EC 5.5.1.4) catalyzes the conversion of glucose 6-phosphate to myo -D(L)-inositol-3(1)-phosphate [20], and (2) inositol monophosphatase (IMPase, EC 3.1.3.25), which dephosphorylates inositol phosphate to yield Ins [21]. Both enzymes have been thoroughly characterized in a number of organisms and several high-resolution 3D protein structures from multiple species have been experimentally determined for these proteins (S1 Table in Supporting Information).…”

Section: Introductionmentioning

confidence: 99%

Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia

Villarreal

Kültz

2015

PLoS ONE

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Myo-inositol (Ins) is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus). Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS) and inositol monophosphatase (IMPase), by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1) were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P), mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P) is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.

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“…The MIB pathway utilizes two enzymes, myo-inositol phosphate synthase (MIPS) and inositol monophosphatase (IMPA), to generate myo-inositol endogenously from glucose-6-phosphate (G-6-P) in a two-step reaction (Geiger and Jin, 2006). The study by Fiol et al (Fiol et al, 2006b) was the first to identify upregulation of MIPS mRNA in response to acute hyperosmotic challenge in tilapia gill, and since then, several studies have confirmed induction of the MIB pathway in other euryhaline species exposed to salinity challenge (Evans and Somero, 2008;Kalujnaia et al, 2009;Kalujnaia et al, 2010;Kalujnaia et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducingmyo-inositol biosynthesis

Gardell

Yang

Sacchi

et al. 2013

Journal of Experimental Biology

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SUMMARYThis study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na + and Cl -concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge.

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The Structure and Mechanism of myo-Inositol-1-Phosphate Synthase

Cited by 27 publications

References 50 publications

Phosphorylation Regulates myo-Inositol-3-phosphate Synthase

Phosphorylation Regulates myo-Inositol-3-phosphate Synthase

Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia

Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducingmyo-inositol biosynthesis

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