1spd
AMYOTROPHIC LATERAL SCLEROSIS AND STRUCTURAL DEFECTS IN CU,ZN SUPEROXIDE DISMUTASE
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OverviewOverview
Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1), occur in patients with the fatal neurodegenerative disorder familial, amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1, coding region revealed that the mutation Ala4 to Val in exon 1 was the, most frequent one; mutations were identified in exons 2, 4, and 5 but not, in the active site region formed by exon 3. The 2.4 A crystal structure of, human SOD, along with two other SOD structures, established that all 12, observed FALS mutant sites alter conserved interactions critical to the, beta-barrel fold and dimer contact, rather than catalysis. Red cells from, heterozygotes had less than 50 percent normal SOD activity, consistent, with a structurally defective SOD dimer. Thus, defective SOD is linked to, motor neuron death and carries implications for understanding and possible, treatment of FALS.
DiseaseDisease
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]
About this StructureAbout this Structure
1SPD is a Single protein structure of sequence from Homo sapiens with CU, ZN and ACE as ligands. Active as Superoxide dismutase, with EC number 1.15.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase., Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP, et al., Science. 1993 Aug 20;261(5124):1047-51. PMID:8351519
Page seeded by OCA on Mon Nov 12 19:16:37 2007