2q7d

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[[Image:2q7d.jpg|left|200px]]<br /><applet load="2q7d" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2q7d.jpg|left|200px]]
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caption="2q7d, resolution 1.60&Aring;" />
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'''Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+'''<br />
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{{Structure
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|PDB= 2q7d |SIZE=350|CAPTION= <scene name='initialview01'>2q7d</scene>, resolution 1.60&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene>
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|ACTIVITY=
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|GENE= ITPK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2Q7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7D OCA].
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2Q7D is a [[Single protein]] structure of sequence from [http://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].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17616525 17616525]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17616525 17616525]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:22:37 2008''

Revision as of 16:22, 20 March 2008


PDB ID 2q7d

Drag the structure with the mouse to rotate
, resolution 1.60Å
Ligands: , and
Gene: ITPK1 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



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


Overview

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.

About this Structure

2Q7D is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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