4RKK
Structure of a product bound phosphatase
Summary for 4RKK
| Entry DOI | 10.2210/pdb4rkk/pdb |
| Related PRD ID | PRD_900009 PRD_900010 PRD_900035 |
| Descriptor | 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) |
| Functional Keywords | dual specificity phosphatase, carbohydrate binding module, phosphatase, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 79733.25 |
| Authors | Vander Kooi, C.W. (deposition date: 2014-10-13, release date: 2015-01-07, Last modification date: 2024-02-28) |
| Primary citation | 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 Cited by 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: 25544560DOI: 10.1016/j.molcel.2014.11.020 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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