4R30

Structure of human laforin dual specificity phosphatase domain

4R30 の概要

• エントリーDOI: 10.2210/pdb4r30/pdb
• 分子名称: Laforin, SULFATE ION, BETA-MERCAPTOETHANOL, ... (4 entities in total)
• 機能のキーワード: dual specificity phosphatase, glucan phosphatase, malin, glycogen, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm . Isoform 1: Endoplasmic reticulum. Isoform 2: Endoplasmic reticulum . Isoform 4: Cytoplasm. Isoform 5: Cytoplasm. Isoform 7: Cytoplasm: O95278
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85311.22

構造登録者

Sankhala, R.S.,Koksal, A.C.,Cingolani, G. (登録日: 2014-08-13, 公開日: 2014-12-31, 最終更新日: 2023-09-20)

主引用文献

Sankhala, R.S.,Koksal, A.C.,Ho, L.,Nitschke, F.,Minassian, B.A.,Cingolani, G.
Dimeric quaternary structure of human laforin.
J.Biol.Chem., 290:4552-4559, 2015

PubMed Abstract: The phosphatase laforin removes phosphate groups from glycogen during biosynthetic activity. Loss-of-function mutations in the gene encoding laforin is the predominant cause of Lafora disease, a fatal form of progressive myoclonic epilepsy. Here, we used hybrid structural methods to determine the molecular architecture of human laforin. We found that laforin adopts a dimeric quaternary structure, topologically similar to the prototypical dual specificity phosphatase VH1. The interface between the laforin carbohydrate-binding module and the dual specificity phosphatase domain generates an intimate substrate-binding crevice that allows for recognition and dephosphorylation of phosphomonoesters of glucose. We identify novel molecular determinants in the laforin active site that help decipher the mechanism of glucan phosphatase activity.

PubMed: 25538239
DOI: 10.1074/jbc.M114.627406

実験手法

X-RAY DIFFRACTION (2.3 Å)