2QB5

Crystal Structure of Human Inositol 1,3,4-Trisphosphate 5/6-Kinase (ITPK1) in Complex with ADP and Mn2+

2QB5 の概要

• エントリーDOI: 10.2210/pdb2qb5/pdb
• 分子名称: Inositol-tetrakisphosphate 1-kinase, SULFATE ION, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: inositol, inositol kinase, kinase, itpk1, inositol 1, 3, 4-5/6-kinase, phosphate, inositol phosphate, inositolphosphate, polyphosphate, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80552.00

構造登録者

Chamberlain, P.P.,Lesley, S.A.,Spraggon, G. (登録日: 2007-06-15, 公開日: 2007-07-03, 最終更新日: 2024-02-21)

主引用文献

Chamberlain, P.P.,Qian, X.,Stiles, A.R.,Cho, J.,Jones, D.H.,Lesley, S.A.,Grabau, E.A.,Shears, S.B.,Spraggon, G.
Integration of inositol phosphate signaling pathways via human ITPK1.
J.Biol.Chem., 282:28117-28125, 2007

PubMed Abstract: 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.

PubMed: 17616525
DOI: 10.1074/jbc.M703121200

実験手法

X-RAY DIFFRACTION (1.8 Å)