Inositol polyphosphate kinase

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Inositol polyphosphate kinase
PDB 1w2f EBI.jpg
Structure of the Inositol 1,4,5-trisphosphate 3-kinase A protein.
Identifiers
SymbolIPK
Pfam PF03770
InterPro IPR005522
SCOP2 1tzd / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Inositol polyphosphate kinase (IPK) is a family of enzymes [1] that have a similar 3-dimensional structure. All members of the family catalyze the transfer of phosphate groups from ATP to various inositol phosphates. Members of the family include inositol-polyphosphate multikinases, inositol-hexakisphosphate kinases, inositol-trisphosphate 3-kinases, and inositol-pentakisphosphate 2-kinase, which is more distantly related to the others [2] [3]

The discovery of the IPK family occurred in 1999, when a combination of biochemistry, sequence analysis, and genetics led to the classification of a family of inositol polyphosphate kinases. [4] [5] In 2005, the first crystal structures of an IPK family protein were published for ITPKA. [6] [7]

Subsequently, structures of the inositol polyphosphate multikinase and various IP6 kinases have expanded our structural understanding for how each enzyme catalyzes its specific reaction(s).

Related Research Articles

Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals.

<span class="mw-page-title-main">Inositol trisphosphate receptor</span> Class of transport proteins

Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca2+ signals characterized by complex patterns relative to both space and time, such as Ca2+ waves and oscillations.

<span class="mw-page-title-main">Inositol phosphate</span>

Inositol phosphates are a group of mono- to hexaphosphorylated inositols. Each form of inositol phosphate is distinguished by the number and position of the phosphate group on the inositol ring.

<span class="mw-page-title-main">Phosphoinositide phospholipase C</span>

Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. These enzymes belong to a larger superfamily of Phospholipase C. Other families of phospholipase C enzymes have been identified in bacteria and trypanosomes. Phospholipases C are phosphodiesterases.

<span class="mw-page-title-main">Inositol pentakisphosphate</span> Chemical compound

Inositol pentakisphosphate is a molecule derived from inositol tetrakisphosphate by adding a phosphate group with the help of Inositol-polyphosphate multikinase (IPMK). It is believed to be one of the many second messengers in the inositol phosphate family. It "is implicated in a wide array of biological and pathophysiological responses, including tumorigenesis, invasion and metastasis, therefore specific inhibitors of the kinase may prove useful in cancer therapy."

<span class="mw-page-title-main">ITPKB</span> Protein-coding gene in the species Homo sapiens

Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.

The enzyme multiple inositol-polyphosphate phosphatase (EC 3.1.3.62) catalyzes the reaction

In enzymology, a diphosphoinositol-pentakisphosphate kinase is an enzyme that catalyzes the chemical reaction

In enzymology, an inositol-pentakisphosphate 2-kinase is an enzyme that catalyzes the chemical reaction

In enzymology, an inositol-tetrakisphosphate 1-kinase is an enzyme that catalyzes the chemical reaction

In enzymology, an inositol-tetrakisphosphate 5-kinase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Inositol-trisphosphate 3-kinase</span> Class of enzymes

Inositol (1,4,5) trisphosphate 3-kinase (EC 2.7.1.127), abbreviated here as ITP3K, is an enzyme that facilitates a phospho-group transfer from adenosine triphosphate to 1D-myo-inositol 1,4,5-trisphosphate. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1D-myo-inositol-1,4,5-trisphosphate 3-phosphotransferase. ITP3K catalyzes the transfer of the gamma-phosphate from ATP to the 3-position of inositol 1,4,5-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate. ITP3K is highly specific for the 1,4,5-isomer of IP3, and it exclusively phosphorylates the 3-OH position, producing Ins(1,3,4,5)P4, also known as inositol tetrakisphosphate or IP4.

<span class="mw-page-title-main">Phospholipase C</span> Class of enzymes

Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.

<span class="mw-page-title-main">ITPKA</span> Protein-coding gene in the species Homo sapiens

Inositol-trisphosphate 3-kinase A is an enzyme that in humans is encoded by the ITPKA gene.

<span class="mw-page-title-main">IHPK2</span> Protein-coding gene in the species Homo sapiens

Inositol hexakisphosphate kinase 2 is an enzyme that in humans is encoded by the IP6K2 gene.

<span class="mw-page-title-main">ITPK1</span> Protein-coding gene in the species Homo sapiens

Inositol-tetrakisphosphate 1-kinase is an enzyme that in humans is encoded by the ITPK1 gene.

<span class="mw-page-title-main">IHPK1</span> Protein-coding gene in the species Homo sapiens

Inositol hexakisphosphate kinase 1 is an enzyme that in humans is encoded by the IP6K1 gene.

Inositol-polyphosphate multikinase is an enzyme with systematic name ATP:1D-myo-inositol-1,4,5-trisphosphate 6-phosphotransferase. This enzyme catalyses the following chemical reaction

inositol-1,3,4-trisphosphate 5/6-kinase is an enzyme with systematic name ATP:1D-myo-inositol 1,3,4-trisphosphate 5-phosphotransferase. This enzyme catalyses the following chemical reaction

The enzyme Inositol-polyphosphate 5-phosphatase (EC 3.1.3.56, systematic name 1D-myo-inositol-1,4,5-trisphosphate 5-phosphohydrolase; other names type I inositol-polyphosphate phosphatase, inositol trisphosphate phosphomonoesterase, InsP3/Ins(1,3,4,5)P4 5-phosphatase, inosine triphosphatase, D-myo-inositol 1,4,5-triphosphate 5-phosphatase, D-myo-inositol 1,4,5-trisphosphate 5-phosphatase, L-myo-inositol 1,4,5-trisphosphate-monoesterase, inositol phosphate 5-phosphomonoesterase, inositol-1,4,5-trisphosphate/1,3,4,5-tetrakisphosphate 5-phosphatase, Ins(1,4,5)P3 5-phosphataseD-myo-inositol(1,4,5)/(1,3,4,5)-polyphosphate 5-phosphatase, inositol 1,4,5-trisphosphate phosphatase, inositol polyphosphate-5-phosphatase, myo-inositol-1,4,5-trisphosphate 5-phosphatase, inositol-1,4,5-trisphosphate 5-phosphatase) catalyses the following reaction

References

  1. "Kinase Family IPK - WikiKinome". kinase.com.
  2. "InterPro".
  3. González B, Baños-Sanz JI, Villate M, Brearley CA, Sanz-Aparicio J (2010). "Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition". Proc Natl Acad Sci U S A. 107 (21): 9608–13. Bibcode:2010PNAS..107.9608G. doi: 10.1073/pnas.0912979107 . PMC   2906834 . PMID   20453199.
  4. Saiardi A, Erdjument-Bromage H, Snowman AM, Tempst P, Snyder SH (1999). "Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases". Curr Biol. 9 (22): 1323–6. doi: 10.1016/s0960-9822(00)80055-x . PMID   10574768.
  5. Odom AR, Stahlberg A, Wente SR, York JD (2000). "A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control". Science. 287 (5460): 2026–9. Bibcode:2000Sci...287.2026O. doi:10.1126/science.287.5460.2026. PMID   10720331.
  6. González B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL (2004). "Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase". Mol Cell. 15 (5): 689–701. doi: 10.1016/j.molcel.2004.08.004 . PMID   15350214.
  7. Miller GJ, Hurley JH (2004). "Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase". Mol Cell. 15 (5): 703–11. doi: 10.1016/j.molcel.2004.08.005 . PMID   15350215.