3ecw

Crystal structure of the ALS-related pathological mutant T54R of human apo Cu,Zn Superoxide Dismutase (SOD1)

spinqualitylabelsall models 3ecw, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ecw is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SODC_HUMAN Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:105400. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms. [:] Function SODC_HUMAN Destroys radicals which are normally produced within the cells and which are toxic to biological systems. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The structural and dynamical properties of the metal-free form of WT human superoxide dismutase 1 (SOD1) and its familial amyotrophic lateral sclerosis (fALS)-related mutants, T54R and I113T, were characterized both in solution, through NMR, and in the crystal, through X-ray diffraction. We found that all 3 X-ray structures show significant structural disorder in 2 loop regions that are, at variance, well defined in the fully-metalated structures. Interestingly, the apo state crystallizes only at low temperatures, whereas all 3 proteins in the metalated form crystallize at any temperature, suggesting that crystallization selects one of the most stable conformations among the manifold adopted by the apo form in solution. Indeed, NMR experiments show that the protein in solution is highly disordered, sampling a large range of conformations. The large conformational variability of the apo state allows the free reduced cysteine Cys-6 to become highly solvent accessible in solution, whereas it is essentially buried in the metalated state and the crystal structures. Such solvent accessibility, together with that of Cys-111, accounts for the tendency to oligomerization of the metal-free state. The present results suggest that the investigation of the solution state coupled with that of the crystal state can provide major insights into SOD1 pathway toward oligomerization in relation to fALS. Structural and dynamic aspects related to oligomerization of apo SOD1 and its mutants.,Banci L, Bertini I, Boca M, Calderone V, Cantini F, Girotto S, Vieru M Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6980-5. Epub 2009 Apr 14. PMID:19369197 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Superoxide dismutase 3D structures

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