4RKK

Structure of a product bound phosphatase

4RKK の概要

• エントリーDOI: 10.2210/pdb4rkk/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900009 PRD_900010 PRD_900035
• 分子名称: Laforin, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: dual specificity phosphatase, carbohydrate binding module, phosphatase, hydrolase
• 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: 79733.25

構造登録者

Vander Kooi, C.W. (登録日: 2014-10-13, 公開日: 2015-01-07, 最終更新日: 2024-02-28)

主引用文献

Raththagala, M.,Brewer, M.K.,Parker, M.W.,Sherwood, A.R.,Wong, B.K.,Hsu, S.,Bridges, T.M.,Paasch, B.C.,Hellman, L.M.,Husodo, S.,Meekins, D.A.,Taylor, A.O.,Turner, B.D.,Auger, K.D.,Dukhande, V.V.,Chakravarthy, S.,Sanz, P.,Woods, V.L.,Li, S.,Vander Kooi, C.W.,Gentry, M.S.
Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.
Mol.Cell, 57:261-272, 2015

PubMed Abstract: Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease.

PubMed: 25544560
DOI: 10.1016/j.molcel.2014.11.020

実験手法

X-RAY DIFFRACTION (2.4 Å)