Structural highlights
Publication Abstract from PubMed
Cu/Zn superoxide dismutase-1 (SOD1) mutations are causative for a subset of amyotrophic lateral sclerosis (ALS) cases. These mutations lead to structural instability, aggregation and ultimately motor neuron death. We have determined crystal structures of SOD1 in complex with a naphthalene-catechol-linked compound which binds with low micro-molar affinity to a site important for oxidative damage-induced aggregation. SOD1 Trp32 oxidation is indeed significantly inhibited by ligand binding. Our work shows how compound linking can be applied successfully to ligand interactions on the SOD1 surface to generate relatively good binding strength. The ligand, positioned in a region important for SOD1 fibrillation, offers the possibility that it, or a similar compound, could prevent the abnormal self-association that drives SOD1 toxicity in ALS.
Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation.,Manjula R, Wright GSA, Strange RW, Padmanabhan B FEBS Lett. 2018 May;592(10):1725-1737. doi: 10.1002/1873-3468.13055. Epub 2018, May 11. PMID:29679384[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Manjula R, Wright GSA, Strange RW, Padmanabhan B. Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation. FEBS Lett. 2018 May;592(10):1725-1737. PMID:29679384 doi:10.1002/1873-3468.13055
