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[[Image:1z2o.gif|left|200px]]<br /><applet load="1z2o" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1z2o, resolution 1.24&Aring;" />
'''Inositol 1,3,4-trisphosphate 5/6-Kinase in complex with mg2+/ADP/Ins(1,3,4,6)P4'''<br />


==Overview==
==Inositol 1,3,4-trisphosphate 5/6-Kinase in complex with mg2+/ADP/Ins(1,3,4,6)P4==
Inositol hexakisphosphate and other inositol high polyphosphates have diverse and critical roles in eukaryotic regulatory pathways. Inositol 1,3,4-trisphosphate 5/6-kinase catalyzes the rate-limiting step in inositol high polyphosphate synthesis in animals. This multifunctional enzyme also has inositol 3,4,5,6-tetrakisphosphate 1-kinase and other activities. The structure of an archetypal family member, from Entamoeba histolytica, has been determined to 1.2 A resolution in binary and ternary complexes with nucleotide, substrate, and product. The structure reveals an ATP-grasp fold. The inositol ring faces ATP edge-on such that the 5- and 6-hydroxyl groups are nearly equidistant from the ATP gamma-phosphate in catalytically productive phosphoacceptor positions and explains the unusual dual site specificity of this kinase. Inositol tris- and tetrakisphosphates interact via three phosphate binding subsites and one solvent-exposed site that could in principle be occupied by 18 different substrates, explaining the mechanisms for the multiple specificities and catalytic activities of this enzyme.
<StructureSection load='1z2o' size='340' side='right'caption='[[1z2o]], [[Resolution|resolution]] 1.24&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1z2o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica_HM-1:IMSS Entamoeba histolytica HM-1:IMSS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z2O FirstGlance]. <br>
1Z2O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Eukaryota Eukaryota] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=I4P:'>I4P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z2O OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.24&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=I4P:(1S,3R,4R,6S)-1,3,4,6-TETRAPKISPHOSPHATE'>I4P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z2o OCA], [https://pdbe.org/1z2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z2o RCSB], [https://www.ebi.ac.uk/pdbsum/1z2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z2o ProSAT]</span></td></tr>
Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase., Miller GJ, Wilson MP, Majerus PW, Hurley JH, Mol Cell. 2005 Apr 15;18(2):201-12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15837423 15837423]
</table>
[[Category: Eukaryota]]
== Function ==
[[Category: Single protein]]
[https://www.uniprot.org/uniprot/ITPK1_ENTH1 ITPK1_ENTH1] Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium.
[[Category: Hurley, J H.]]
== Evolutionary Conservation ==
[[Category: Majerus, P W.]]
[[Image:Consurf_key_small.gif|200px|right]]
[[Category: Miller, G J.]]
Check<jmol>
[[Category: Wilson, M P.]]
  <jmolCheckbox>
[[Category: ADP]]
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z2/1z2o_consurf.spt"</scriptWhenChecked>
[[Category: I4P]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
[[Category: MG]]
    <text>to colour the structure by Evolutionary Conservation</text>
[[Category: atp-grasp]]
  </jmolCheckbox>
[[Category: inositol phosphate kinase]]
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1z2o ConSurf].
 
<div style="clear:both"></div>
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:11:31 2008''
__TOC__
</StructureSection>
[[Category: Entamoeba histolytica HM-1:IMSS]]
[[Category: Large Structures]]
[[Category: Hurley JH]]
[[Category: Majerus PW]]
[[Category: Miller GJ]]
[[Category: Wilson MP]]

Latest revision as of 12:02, 14 February 2024

Inositol 1,3,4-trisphosphate 5/6-Kinase in complex with mg2+/ADP/Ins(1,3,4,6)P4Inositol 1,3,4-trisphosphate 5/6-Kinase in complex with mg2+/ADP/Ins(1,3,4,6)P4

Structural highlights

1z2o is a 1 chain structure with sequence from Entamoeba histolytica HM-1:IMSS. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.24Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ITPK1_ENTH1 Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

1z2o, resolution 1.24Å

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