PDBsum entry 5o3y

Oxidoreductase

PDB id: 5o3y

Contents

Protein chains

153 a.a.

Ligands

9JK ×2

SO4 ×2

Metals

_ZN ×4

Waters ×314

PDB id:

5o3y

Name:

Oxidoreductase

Title:

Sod1 bound to ebsulfur

Structure:

Superoxide dismutase [cu-zn]. Chain: a, f. Synonym: superoxide dismutase 1,hsod1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.30Å R-factor: 0.153 R-free: 0.186

Authors:

M.J.Capper,G.S.A.Wright,S.V.Antonyuk,S.S.Hasnain

Key ref:

M.J.Capper et al. (2018). The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation. Nat Commun, 9, 1693. PubMed id: 29703933

Date:

25-May-17 Release date: 13-Jun-18

Protein chains

P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn] from Homo sapiens

Seq: 154 a.a.

Struc: 153 a.a.

Enzyme reactions

• Enzyme class: E.C.1.15.1.1 - superoxide dismutase.
• Reaction: 2 superoxide + 2 H⁺ = H2O2 + O2
• Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Nat Commun 9:1693 (2018)

PubMed id: 29703933

The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation.

M.J.Capper, G.S.A.Wright, L.Barbieri, E.Luchinat, E.Mercatelli, L.McAlary, J.J.Yerbury, P.M.O'Neill, S.V.Antonyuk, L.Banci, S.S.Hasnain.

ABSTRACT

Superoxide dismutase-1 (SOD1) mutants, including those with unaltered enzymatic activity, are known to cause amyotrophic lateral sclerosis (ALS). Several destabilizing factors contribute to pathogenicity including a reduced ability to complete the normal maturation process which comprises folding, metal cofactor acquisition, intra-subunit disulphide bond formation and dimerization. Immature SOD1 forms toxic oligomers and characteristic large insoluble aggregates within motor system cells. Here we report that the cysteine-reactive molecule ebselen efficiently confers the SOD1 intra-subunit disulphide and directs correct SOD1 folding, depopulating the globally unfolded precursor associated with aggregation and toxicity. Assisted formation of the unusual SOD1 cytosolic disulphide bond could have potential therapeutic applications. In less reducing environments, ebselen forms a selenylsulphide with Cys111 and restores the monomer-dimer equilibrium of A4V SOD1 to wild-type. Ebselen is therefore a potent bifunctional pharmacological chaperone for SOD1 that combines properties of the SOD1 chaperone hCCS and the recently licenced antioxidant drug, edaravone.