2q7d

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Revision as of 21:24, 12 November 2007

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spinqualitylabelsall models 2q7d, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 with MN, SO4 and ANP as ligands. 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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