4A7T
Structure of human I113T SOD1 mutant complexed with isoproteranol in the p21 space group
Summary for 4A7T
| Entry DOI | 10.2210/pdb4a7t/pdb |
| 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 2V0A 2VR6 2VR7 2VR8 2WKO 2WYT 2WYZ 2WZ0 2WZ5 2WZ6 2XJK 2XJL 4A7G 4A7Q 4A7R 4A7S 4A7U 4A7V 4SOD |
| Descriptor | SUPEROXIDE DISMUTASE [CU-ZN], ISOPRENALINE, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | oxidoreductase, amyotrophic lateral sclerosis, antioxidant, disease mutation, metal-binding, zn superoxide dismutase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cytoplasm: P00441 |
| Total number of polymer chains | 2 |
| Total formula weight | 33447.56 |
| Authors | Wright, G.S.A.,Kershaw, N.M.,Antonyuk, S.V.,Strange, R.W.,ONeil, P.M.,Hasnain, S.S. (deposition date: 2011-11-14, release date: 2012-11-28, Last modification date: 2024-11-06) |
| Primary citation | Wright, G.S.A.,Antonyuk, S.V.,Kershaw, N.M.,Strange, R.W.,Hasnain, S.S. Ligand Binding and Aggregation of Pathogenic Sod1. Nat.Commun., 4:1758-, 2013 Cited by PubMed Abstract: Mutations in the gene encoding Cu/Zn superoxide dismutase-1 cause amyotrophic lateral sclerosis. Superoxide dismutase-1 mutations decrease protein stability and promote aggregation. The mutant monomer is thought to be an intermediate in the pathway from the superoxide dismutase-1 dimer to aggregate. Here we find that the monomeric copper-apo, zinc-holo protein is structurally perturbed and the apo-protein aggregates without reattainment of the monomer-dimer equilibrium. Intervention to stabilize the superoxide dismutase-1 dimer and inhibit aggregation is regarded as a potential therapeutic strategy. We describe protein-ligand interactions for two compounds, Isoproterenol and 5-fluorouridine, highlighted as superoxide dismutase-1 stabilizers. We find both compounds interact with superoxide dismutase-1 at a key region identified at the core of the superoxide dismutase-1 fibrillar aggregates, β-barrel loop II-strand 3, rather than the proposed dimer interface site. This illustrates the need for direct structural observations when developing compounds for protein-targeted therapeutics. PubMed: 23612299DOI: 10.1038/NCOMMS2750 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
Download full validation report
