2v0a

Atomic resolution crystal structure of Human Superoxide Dismutase

spinqualitylabelsall models 2v0a, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v0a is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CU, SO4, ZN Related: 1azv, 1ba9, 1dsw, 1fun, 1hl4, 1hl5, 1kmg, 1l3n, 1mfm, 1n18, 1n19, 1oez, 1ozt, 1ozu, 1p1v, 1ptz, 1pu0, 1rk7, 1sos, 1spd, 1uxl, 1uxm, 2af2, 2c9s, 2c9u, 2c9v, 4sod 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 Mutations of the gene encoding Cu-Zn superoxide dismutase (SOD1) cause 20% of the familial cases of the progressive neurodegenerative disease ALS. A growing body of evidence suggests that in familial ALS (FALS) it is the molecular behavior of the metal-depleted SOD1 dimer that leads to a gain of toxic properties by misfolding, unfolding, and aggregation. Structural studies have so far provided static snapshots on the behavior of the wild-type enzyme and some of the FALS mutants. New approaches are required to map out the structural trajectories of the molecule. Here, using our 1.15-A resolution structure of fully metallated human SOD1 and highly parallelized molecular dynamics code on a high-performance capability computer, we have undertaken molecular dynamics calculations to 4,000 ps to reveal the first stages of misfolding caused by metal deletion. Large spatial and temporal fluctuations of the "electrostatic" and "Zn-binding" loops adjacent to the metal-binding sites are observed in the apo-enzyme relative to the fully metallated dimer. These early misfolding events expose the beta-barrels of the dimer to the external environment, allowing close interactions with adjacent molecules. Protection of the beta-edge of the protein can be partially restored by incorporating a single Zn molecule per dimer. These calculations reveal an essential step in the formation of the experimentally observed self-aggregations of metal-depleted FALS mutant SOD1. This result also has implications for the role of demetallated wild-type SOD1 in sporadic cases of ALS, for which the molecular cause still remains undiscovered. Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase.,Strange RW, Yong CW, Smith W, Hasnain SS Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10040-4. Epub 2007 Jun 4. PMID:17548825 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Superoxide dismutase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA