2q7d: Difference between revisions

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<StructureSection load='2q7d' size='340' side='right'caption='[[2q7d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='2q7d' size='340' side='right'caption='[[2q7d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2q7d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q7D FirstGlance]. <br>
<table><tr><td colspan='2'>[[2q7d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q7D FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITPK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q7d OCA], [https://pdbe.org/2q7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q7d RCSB], [https://www.ebi.ac.uk/pdbsum/2q7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q7d ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q7d OCA], [https://pdbe.org/2q7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q7d RCSB], [https://www.ebi.ac.uk/pdbsum/2q7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q7d ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/ITPK1_HUMAN ITPK1_HUMAN]] 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. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. 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. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain.<ref>PMID:11533064</ref> <ref>PMID:11909533</ref> <ref>PMID:12925536</ref> <ref>PMID:17616525</ref>
[https://www.uniprot.org/uniprot/ITPK1_HUMAN ITPK1_HUMAN] 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. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. 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. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain.<ref>PMID:11533064</ref> <ref>PMID:11909533</ref> <ref>PMID:12925536</ref> <ref>PMID:17616525</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=2q7d ConSurf].
</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=2q7d ConSurf].
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== Publication Abstract from PubMed ==
Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a reversible, poly-specific inositol phosphate kinase that has been implicated as a modifier gene in cystic fibrosis. Upon activation of phospholipase C at the plasma membrane, inositol 1,4,5-trisphosphate enters the cytosol and is inter-converted by an array of kinases and phosphatases into other inositol phosphates with diverse and critical cellular activities. In mammals it has been established that inositol 1,3,4-trisphosphate, produced from inositol 1,4,5-trisphosphate, lies in a branch of the metabolic pathway that is separate from inositol 3,4,5,6-tetrakisphosphate, which inhibits plasma membrane chloride channels. We have determined the molecular mechanism for communication between these two pathways, showing that phosphate is transferred between inositol phosphates via ITPK1-bound nucleotide. Intersubstrate phosphate transfer explains how competing substrates are able to stimulate each others' catalysis by ITPK1. We further show that these features occur in the human protein, but not in plant or protozoan homologues. The high resolution structure of human ITPK1 identifies novel secondary structural features able to impart substrate selectivity and enhance nucleotide binding, thereby promoting intersubstrate phosphate transfer. Our work describes a novel mode of substrate regulation and provides insight into the enzyme evolution of a signaling mechanism from a metabolic role.
Integration of inositol phosphate signaling pathways via human ITPK1.,Chamberlain PP, Qian X, Stiles AR, Cho J, Jones DH, Lesley SA, Grabau EA, Shears SB, Spraggon G J Biol Chem. 2007 Sep 21;282(38):28117-25. Epub 2007 Jul 6. PMID:17616525<ref>PMID:17616525</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2q7d" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chamberlain, P P]]
[[Category: Chamberlain PP]]
[[Category: Lesley, S A]]
[[Category: Lesley SA]]
[[Category: Spraggon, G]]
[[Category: Spraggon G]]
[[Category: 4-5/6-kinase]]
[[Category: Inositol]]
[[Category: Inositol 1]]
[[Category: Inositol kinase]]
[[Category: Inositol phosphate]]
[[Category: Inositolphosphate]]
[[Category: Itpk1]]
[[Category: Kinase]]
[[Category: Phosphate]]
[[Category: Polyphosphate]]
[[Category: Transferase]]

Latest revision as of 09:14, 21 February 2024

Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+

2q7d, resolution 1.60Å

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