5E3S

Crystal structure of Phosphatidylinositol-4-phosphate 5-kinase

5E3S の概要

• エントリーDOI: 10.2210/pdb5e3s/pdb
• 関連するPDBエントリー: 5E3T 5E3U
• 分子名称: Phosphatidylinositol-4-phosphate 5-kinase, type I, alpha (1 entity in total)
• 機能のキーワード: kinase, transferase
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42255.42

構造登録者

Muftuoglu, Y. (登録日: 2015-10-04, 公開日: 2016-07-20, 最終更新日: 2024-03-06)

主引用文献

Muftuoglu, Y.,Xue, Y.,Gao, X.,Wu, D.,Ha, Y.
Mechanism of substrate specificity of phosphatidylinositol phosphate kinases.
Proc.Natl.Acad.Sci.USA, 113:8711-8716, 2016

PubMed Abstract: The phosphatidylinositol phosphate kinase (PIPK) family of enzymes is primarily responsible for converting singly phosphorylated phosphatidylinositol derivatives to phosphatidylinositol bisphosphates. As such, these kinases are central to many signaling and membrane trafficking processes in the eukaryotic cell. The three types of phosphatidylinositol phosphate kinases are homologous in sequence but differ in catalytic activities and biological functions. Type I and type II kinases generate phosphatidylinositol 4,5-bisphosphate from phosphatidylinositol 4-phosphate and phosphatidylinositol 5-phosphate, respectively, whereas the type III kinase produces phosphatidylinositol 3,5-bisphosphate from phosphatidylinositol 3-phosphate. Based on crystallographic analysis of the zebrafish type I kinase PIP5Kα, we identified a structural motif unique to the kinase family that serves to recognize the monophosphate on the substrate. Our data indicate that the complex pattern of substrate recognition and phosphorylation results from the interplay between the monophosphate binding site and the specificity loop: the specificity loop functions to recognize different orientations of the inositol ring, whereas residues flanking the phosphate binding Arg244 determine whether phosphatidylinositol 3-phosphate is exclusively bound and phosphorylated at the 5-position. This work provides a thorough picture of how PIPKs achieve their exquisite substrate specificity.

PubMed: 27439870
DOI: 10.1073/pnas.1522112113

実験手法

X-RAY DIFFRACTION (3.1 Å)