PDBsum entry 4ff9

Oxidoreductase

PDB id: 4ff9

Contents

Protein chain

153 a.a.

Ligands

CYS

Metals

_CU ×2

_ZN ×2

Waters ×24

PDB id:

4ff9

Name:

Oxidoreductase

Title:

Crystal structure of cysteinylated wt sod1.

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.

Resolution:

2.50Å R-factor: 0.282 R-free: 0.335

Authors:

J.R.Auclair,H.R.Brodkin,J.A.D'Aquino,D.Ringe,G.A.Petsko,J.N.Agar

Key ref:

J.R.Auclair et al. (2013). Structural consequences of cysteinylation of Cu/Zn-superoxide dismutase. Biochemistry, 52, 6145-6150. PubMed id: 23919400 DOI: 10.1021/bi400613h

Date:

31-May-12 Release date: 04-Sep-13

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

DOI no: 10.1021/bi400613h

Biochemistry 52:6145-6150 (2013)

PubMed id: 23919400

Structural consequences of cysteinylation of Cu/Zn-superoxide dismutase.

J.R.Auclair, H.R.Brodkin, J.A.D'Aquino, G.A.Petsko, D.Ringe, J.N.Agar.

ABSTRACT

The metalloenzyme Cu/Zn-superoxide dismutase (SOD1) catalyzes the reduction of superoxide anions into molecular oxygen and hydrogen peroxide. Hydrogen peroxide can oxidize SOD1, resulting in aberrant protein conformational changes, disruption of SOD1 function, and DNA damage. Cells may have evolved mechanisms of regulation that prevent such oxidation. We observed that cysteinylation of cysteine 111 (Cys111) of SOD1 prevents oxidation by peroxide (DOI 10.1021/bi4006122 ). In this article, we characterize cysteinylated SOD1 using differential scanning fluorometry and X-ray crystallography. The stoichiometry of binding was one cysteine per SOD1 dimer, and there does not appear to be free volume for a second cysteine without disrupting the dimer interface. Much of the three-dimensional structure of SOD1 is unaffected by cysteinylation. However, local conformational changes are observed in the cysteinylated monomer that include changes in conformation of the electrostatic loop (loop VII; residues 133-144) and the dimer interface (loop VI; residues 102-115). In addition, our data shows how cysteinylation precludes oxidation of cysteine 111 and suggests possible cross-talk between the dimer interface and the electrostatic loop.