3V0H

Crystal structure of Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP), residues 241-576(C363S), complexed with D-MYO-inositol-1,4,5-triphosphate

3V0H の概要

• エントリーDOI: 10.2210/pdb3v0h/pdb
• 関連するPDBエントリー: 3V0D 3V0E 3V0F 3V0G 3V0I 3V0J
• 分子名称: Voltage-sensor containing phosphatase, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: ptp, c2, phosphatase, hydrolase
• 由来する生物種: Ciona intestinalis (Transparent sea squirt)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79336.35

構造登録者

Liu, L.,Kohout, S.C.,Xu, Q.,Muller, S.,Kimberlin, C.,Isacoff, E.Y.,Minor, D.L. (登録日: 2011-12-08, 公開日: 2012-05-09, 最終更新日: 2023-09-13)

主引用文献

Liu, L.,Kohout, S.C.,Xu, Q.,Muller, S.,Kimberlin, C.R.,Isacoff, E.Y.,Minor, D.L.
A glutamate switch controls voltage-sensitive phosphatase function.
Nat.Struct.Mol.Biol., 19:633-641, 2012

PubMed Abstract: The Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) couples a voltage-sensing domain (VSD) to a lipid phosphatase that is similar to the tumor suppressor PTEN. How the VSD controls enzyme function has been unclear. Here, we present high-resolution crystal structures of the Ci-VSP enzymatic domain that reveal conformational changes in a crucial loop, termed the 'gating loop', that controls access to the active site by a mechanism in which residue Glu411 directly competes with substrate. Structure-based mutations that restrict gating loop conformation impair catalytic function and demonstrate that Glu411 also contributes to substrate selectivity. Structure-guided mutations further define an interaction between the gating loop and linker that connects the phosphatase to the VSD for voltage control of enzyme activity. Together, the data suggest that functional coupling between the gating loop and the linker forms the heart of the regulatory mechanism that controls voltage-dependent enzyme activation.

PubMed: 22562138
DOI: 10.1038/nsmb.2289

実験手法

X-RAY DIFFRACTION (1.85 Å)