PDBsum entry: 2atf

Oxidoreductase

PDB id: 2atf

Contents

Protein chain

186 a.a. *

Ligands

EDO

Metals

_NI

Waters ×188

* Residue conservation analysis

PDB id:

2atf

Name:

Oxidoreductase

Title:

X-ray structure of cysteine dioxygenase type i from mus musculus mm.241056

Structure:

Cysteine dioxygenase type i. Chain: a. Synonym: cdo, cdo-i. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: cdo1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.75Å R-factor: 0.181 R-free: 0.216

Authors:

G.E.Wesenberg,G.N.Phillips Jr.,J.G.Mccoy,E.Bitto, C.A.Bingman,S.T.M.Allard,Center For Eukaryotic Structural Genomics (Cesg)

Key ref:

J.G.McCoy et al. (2006). Structure and mechanism of mouse cysteine dioxygenase. Proc Natl Acad Sci U S A, 103, 3084-3089. PubMed id: 16492780 DOI: 10.1073/pnas.0509262103

Date:

24-Aug-05 Release date: 18-Oct-05

Protein chain

P60334  (CDO1_MOUSE) -  Cysteine dioxygenase type 1

Seq: 200 a.a.

Struc: 186 a.a.

Enzyme reactions

• Enzyme class: E.C.1.13.11.20 - Cysteine dioxygenase.
• Reaction: L-cysteine + O₂ = 3-sulfinoalanine
• Cofactor: Iron; NAD(P)H

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

 Gene Ontology (GO) functional annotation 

• Cellular component: plasma membrane (2 terms)
• Biological process: oxidation reduction (12 terms)
• Biochemical function: oxidoreductase activity (6 terms)

reference

DOI no: 10.1073/pnas.0509262103

Proc Natl Acad Sci U S A 103:3084-3089 (2006)

PubMed id: 16492780

Structure and mechanism of mouse cysteine dioxygenase.

J.G.McCoy, L.J.Bailey, E.Bitto, C.A.Bingman, D.J.Aceti, B.G.Fox, G.N.Phillips.

ABSTRACT

Cysteine dioxygenase (CDO) catalyzes the oxidation of l-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 Angstroms. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical beta-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme.

Selected figure(s)

Figure 3.
Fig. 3. CDO active site contoured at 1.2 . The metal is shown as a gray sphere; His-86, -88, and -140 are the metal ligands. Three additional coordination sites are occupied by water (red spheres). Cys-93 and Tyr-157 are covalently linked, and the hydroxyl group of Tyr-157 is 4.4 Å from the metal. Other conserved active-site residues are also shown.

Figure 5.
Fig. 5. Mechanism for CDO reaction. (A) Resting Fe(II) state. (B) Substrate coordination by sulfur and nitrogen. (C) O[2] coordination, forming a ternary Fe(III)-superoxo complex. (D) The bound sulfur acquires partial cation-radical character, which can be stabilized by the adjacent negative charge on Tyr-157. (E) Combination of bound sulfur and Fe(III)-superoxo to give a cyclic peroxo intermediate. (F) O–O bond breakage to form a sulfoxy cation and metal-bound activated oxygen. (G) Transfer of the metal-bound activated oxygen to form product, cysteine sulfinic acid (CSA).

Figures were selected by an automated process.