Enzymes
UniProtKB help_outline | 2,156 proteins |
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- Name help_outline 3,5-bis(diphospho)-1D-myo-inositol 1,2,4,6-tetrakisphosphate Identifier CHEBI:140372 Charge -13 Formula C6H7O30P8 InChIKeyhelp_outline HHQOOERQSFJGEP-ZSIQDKGESA-A SMILEShelp_outline [C@@H]1(OP(=O)([O-])[O-])[C@@H](OP(=O)([O-])OP([O-])([O-])=O)[C@H](OP(=O)([O-])[O-])[C@@H](OP(=O)([O-])OP([O-])(O)=O)[C@@H](OP(=O)([O-])[O-])[C@H]1OP(=O)([O-])[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,264 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate Identifier CHEBI:140374 Charge -13 Formula C6H6O27P7 InChIKeyhelp_outline UPHPWXPNZIOZJL-PTQMNWPWSA-A SMILEShelp_outline [C@@H]1(OP(=O)([O-])[O-])[C@@H](OP(=O)([O-])[O-])[C@H](OP(=O)([O-])[O-])[C@@H](OP(=O)([O-])OP([O-])([O-])=O)[C@@H](OP(=O)([O-])[O-])[C@H]1OP(=O)([O-])[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,002 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:56312 | RHEA:56313 | RHEA:56314 | RHEA:56315 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase.
Safrany S.T., Caffrey J.J., Yang X., Bembenek M.E., Moyer M.B., Burkhart W.A., Shears S.B.
Diphosphoinositol pentakisphosphate (PP-InsP5 or 'InsP7') and bisdiphosphoinositol tetrakisphosphate ([PP]2-InsP4 or 'InsP8') are the most highly phosphorylated members of the inositol-based cell signaling family. We have purified a rat hepatic diphosphoinositol polyphosphate phosphohydrolase (DIP ... >> More
Diphosphoinositol pentakisphosphate (PP-InsP5 or 'InsP7') and bisdiphosphoinositol tetrakisphosphate ([PP]2-InsP4 or 'InsP8') are the most highly phosphorylated members of the inositol-based cell signaling family. We have purified a rat hepatic diphosphoinositol polyphosphate phosphohydrolase (DIPP) that cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (Km = 340 nM) and [PP]2-InsP4 (Km = 34 nM). Inositol hexakisphophate (InsP6) was not a substrate, but it inhibited metabolism of both [PP]2-InsP4 and PP-InsP5 (IC50 = 0.2 and 3 microM, respectively). Microsequencing of DIPP revealed a 'MutT' domain, which in other contexts guards cellular integrity by dephosphorylating 8-oxo-dGTP, which causes AT to CG transversion mutations. The MutT domain also metabolizes some nucleoside phosphates that may play roles in signal transduction. The rat DIPP MutT domain is conserved in a novel recombinant human uterine DIPP. The nucleotide sequence of the human DIPP cDNA was aligned to chromosome 6; the candidate gene contains at least four exons. The dependence of DIPP's catalytic activity upon its MutT domain was confirmed by mutagenesis of a conserved glutamate residue. DIPP's low molecular size, Mg2+ dependency and catalytic preference for phosphoanhydride bonds are also features of other MutT-type proteins. Because overlapping substrate specificity is a feature of this class of proteins, our data provide new directions for future studies of higher inositol phosphates. << Less
EMBO J. 17:6599-6607(1998) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Arabidopsis PFA-DSP-Type Phosphohydrolases Target Specific Inositol Pyrophosphate Messengers.
Gaugler P., Schneider R., Liu G., Qiu D., Weber J., Schmid J., Jork N., Haener M., Ritter K., Fernandez-Rebollo N., Giehl R.F.H., Trung M.N., Yadav R., Fiedler D., Gaugler V., Jessen H.J., Schaaf G., Laha D.
Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With a cyclic array of phosphate esters and diphosphate groups around <i>myo</i>-inositol, these molecular messengers possess the highest ch ... >> More
Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With a cyclic array of phosphate esters and diphosphate groups around <i>myo</i>-inositol, these molecular messengers possess the highest charge density found in nature. Recent work deciphering inositol pyrophosphate biosynthesis in <i>Arabidopsis</i> revealed important functions of these messengers in nutrient sensing, hormone signaling, and plant immunity. However, despite the rapid hydrolysis of these molecules in plant extracts, very little is known about the molecular identity of the phosphohydrolases that convert these messengers back to their inositol polyphosphate precursors. Here, we investigate whether <i>Arabidopsis</i> Plant and Fungi Atypical Dual Specificity Phosphatases (PFA-DSP1-5) catalyze inositol pyrophosphate phosphohydrolase activity. We find that recombinant proteins of all five <i>Arabidopsis</i> PFA-DSP homologues display phosphohydrolase activity with a high specificity for the 5-β-phosphate of inositol pyrophosphates and only minor activity against the β-phosphates of 4-InsP<sub>7</sub> and 6-InsP<sub>7</sub>. We further show that heterologous expression of <i>Arabidopsis</i> PFA-DSP1-5 rescues wortmannin sensitivity and deranged inositol pyrophosphate homeostasis caused by the deficiency of the PFA-DSP-type inositol pyrophosphate phosphohydrolase Siw14 in yeast. Heterologous expression in <i>Nicotiana benthamiana</i> leaves provided evidence that <i>Arabidopsis</i> PFA-DSP1 also displays 5-β-phosphate-specific inositol pyrophosphate phosphohydrolase activity <i>in planta</i>. Our findings lay the biochemical basis and provide the genetic tools to uncover the roles of inositol pyrophosphates in plant physiology and plant development. << Less
Biochemistry 61:1213-1227(2022) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Structural and biochemical characterization of Siw14: A protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates.
Wang H., Gu C., Rolfes R.J., Jessen H.J., Shears S.B.
Inositol pyrophosphates (PP-InsPs) are "energetic" intracellular signals that are ubiquitous in animals, plants, and fungi; structural and biochemical characterization of PP-InsP metabolic enzymes provides insight into their evolution, reaction mechanisms, and regulation. Here, we describe the 2.3 ... >> More
Inositol pyrophosphates (PP-InsPs) are "energetic" intracellular signals that are ubiquitous in animals, plants, and fungi; structural and biochemical characterization of PP-InsP metabolic enzymes provides insight into their evolution, reaction mechanisms, and regulation. Here, we describe the 2.35-Å-resolution structure of the catalytic core of Siw14, a 5-PP-InsP phosphatase from <i>Saccharomyces cerevisiae</i> and a member of the protein tyrosine-phosphatase (PTP) superfamily. Conclusions that we derive from structural data are supported by extensive site-directed mutagenesis and kinetic analyses, thereby attributing new functional significance to several key residues. We demonstrate the high activity and exquisite specificity of Siw14 for the 5-diphosphate group of PP-InsPs. The three structural elements that demarcate a 9.2-Å-deep substrate-binding pocket each have spatial equivalents in PTPs, but we identify how these are specialized for Siw14 to bind and hydrolyze the intensely negatively charged PP-InsPs. (<i>a</i>) The catalytic P-loop with the C<i>X</i><sub>5</sub>R(S/T) PTP motif contains additional, positively charged residues. (<i>b</i>) A loop between the α5 and α6 helices, corresponding to the Q-loop in PTPs, contains a lysine and an arginine that extend into the catalytic pocket due to displacement of the α5 helix orientation through intramolecular crowding caused by three bulky, hydrophobic residues. (<i>c</i>) The general-acid loop in PTPs is replaced in Siw14 with a flexible loop that does not use an aspartate or glutamate as a general acid. We propose that an acidic residue is not required for phosphoanhydride hydrolysis. << Less
J. Biol. Chem. 293:6905-6914(2018) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.