3LWT

Crystal structure of the Yeast Sac1: Implications for its phosphoinositide phosphatase function

3LWT の概要

• エントリーDOI: 10.2210/pdb3lwt/pdb
• 分子名称: Phosphoinositide phosphatase SAC1 (2 entities in total)
• 機能のキーワード: sac1, sac3/fig4, phosphoinositide phosphatase, lipid metabolism, endoplasmic reticulum, hydrolase, membrane, transmembrane
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass membrane protein : P32368
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57741.45

構造登録者

Mao, Y.,Manford, A.,Xia, T.,Saxena, A.K.,Stefan, C.,Hu, F.,Emr, S.D. (登録日: 2010-02-24, 公開日: 2010-05-05, 最終更新日: 2024-02-21)

主引用文献

Manford, A.,Xia, T.,Saxena, A.K.,Stefan, C.,Hu, F.,Emr, S.D.,Mao, Y.
Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function.
Embo J., 29:1489-1498, 2010

PubMed Abstract: Sac family phosphoinositide (PI) phosphatases are an essential family of CX(5)R(T/S)-based enzymes, involved in numerous aspects of cellular function such as PI homeostasis, cellular signalling, and membrane trafficking. Genetic deletions of several Sac family members result in lethality in animal models and mutations of the Sac3 gene have been found in human hereditary diseases. In this study, we report the crystal structure of a founding member of this family, the Sac phosphatase domain of yeast Sac1. The 2.0 A resolution structure shows that the Sac domain comprises of two closely packed sub-domains, a novel N-terminal sub-domain and the PI phosphatase catalytic sub-domain. The structure further shows a striking conformation of the catalytic P-loop and a large positively charged groove at the catalytic site. These findings suggest an unusual mechanism for its dephosphorylation function. Homology structural modeling of human Fig4/Sac3 allows the mapping of several disease-related mutations and provides a framework for the understanding of the molecular mechanisms of human diseases.

PubMed: 20389282
DOI: 10.1038/emboj.2010.57

実験手法

X-RAY DIFFRACTION (1.956 Å)