1dsw | pdb_00001dsw

THE SOLUTION STRUCTURE OF A MONOMERIC, REDUCED FORM OF HUMAN COPPER, ZINC SUPEROXIDE DISMUTASE BEARING THE SAME CHARGE AS THE NATIVE PROTEIN

spinqualitylabelsall models 1dsw, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1dsw is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CU, ZN Activity: Superoxide dismutase, with EC number 1.15.1.1 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 solution structure of a mutated (Phe50Glu, Gly51Glu, Val148Lys, Ile151Lys), reduced, monomeric form of human copper,zinc superoxide dismutase (SOD; 153 amino acids) has been determined through 2237 meaningful nuclear Overhauser enhancements, out of 2492, and 43 dihedral angle constraints. A characteristic of this mutant is that of having the same overall charge as the dimeric protein, but an activity of only 20% with respect to wild-type SOD. This protein, at variance with a previously characterized monomeric form (Phe50Glu, Gly51Glu, Glu133Gln), does not contain mutations in the active site. Therefore, its characterization allows us to understand the structural changes independently induced by the monomerization and by the active site mutation. The family of 36 conformers, which have a target function with respect to the experimental constraints lower than 1.5 A2, has RMSD values with respect to the average structure of 0.94 +/- 0.14 A2 and 1.50 +/- 0.14 A2 for the backbone and the heavy atoms, respectively. The overall folding, which includes the classical eight-stranded Greek-key beta-barrel and a short alpha-helix, is very close to that of the previously characterized monomeric mutant E133QM2SOD and to that of wild-type SOD. The region involved in the subunit-subunit interactions in the dimeric protein is confirmed to be disordered in the monomeric species. It is also observed that a sizable rearrangement of the charged groups of the electrostatic loop and of Arg143 takes place in the monomeric species. The width of the active site channel, both at its entrance and at the bottleneck of the active site, is discussed in the light of the influence on the enzymatic activity and the latter with respect to the overall charge. It is also confirmed that the NH proton of His63 shields the Cu(I) from the bulk solvent, thus supporting the suggestion that superoxide may interact with the reduced metal ion in an outer-sphere fashion. The solution structure of a monomeric, reduced form of human copper,zinc superoxide dismutase bearing the same charge as the native protein.,Banci L, Bertini I, Del Conte R, Fadin R, Mangani S, Viezzoli MS J Biol Inorg Chem. 1999 Dec;4(6):795-803. PMID:10631612 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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