1M7R

Crystal Structure of Myotubularin-related Protein-2 (MTMR2) Complexed with Phosphate

Summary for 1M7R

• Entry DOI: 10.2210/pdb1m7r/pdb
• Related: 1LW3
• Descriptor: Myotubularin-related Protein-2, PHOSPHATE ION (3 entities in total)
• Functional Keywords: protein-phosphate complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q13614
• Total number of polymer chains: 2
• Total formula weight: 150393.37

Authors

Begley, M.J.,Taylor, G.S.,Kim, S.-A.,Veine, D.M.,Dixon, J.E.,Stuckey, J.A. (deposition date: 2002-07-22, release date: 2003-10-07, Last modification date: 2024-02-14)

Primary citation

Begley, M.J.,Taylor, G.S.,Kim, S.-A.,Veine, D.M.,Dixon, J.E.,Stuckey, J.A.
Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome
Mol.Cell, 12:1391-1402, 2003

PubMed Abstract: Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in members of the myotubularin family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. The crystal structure of a representative member of this family, MTMR2, reveals a phosphatase domain that is structurally unique among PTPs. A series of mutants are described that exhibit altered enzymatic activity and provide insight into the specificity of myotubularin phosphatases toward phosphoinositide substrates. The structure also reveals that the GRAM domain, found in myotubularin family phosphatases and predicted to occur in approximately 180 proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. Finally, the MTMR2 structure will serve as a model for other members of the myotubularin family and provide a framework for understanding the mechanism whereby mutations in these proteins lead to disease.

PubMed: 14690594
DOI: 10.1016/S1097-2765(03)00486-6

Experimental method

X-RAY DIFFRACTION (2.6 Å)