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| | {{STRUCTURE_2q7d| PDB=2q7d | SCENE= }} | | {{STRUCTURE_2q7d| PDB=2q7d | SCENE= }} |
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| - | '''Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+'''
| + | ===Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17616525}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17616525 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17616525}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Polyphosphate]] | | [[Category: Polyphosphate]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:28:41 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:34:09 2008'' |
Revision as of 04:34, 28 July 2008
Template:STRUCTURE 2q7d
Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-kinase (ITPK1) in complex with AMPPNP and Mn2+
Template:ABSTRACT PUBMED 17616525
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
Page seeded by OCA on Mon Jul 28 07:34:09 2008
