PDBsum entry 2ic1

Oxidoreductase

PDB id: 2ic1

Contents

Protein chain

185 a.a. *

Ligands

CYS ×2

Metals

FE2

Waters ×131

* Residue conservation analysis

PDB id:

2ic1

Name:

Oxidoreductase

Title:

Crystal structure of human cysteine dioxygenase in complex with substrate cysteine

Structure:

Cysteine dioxygenase type 1. Chain: a. Synonym: cysteine dioxygenase type i, cdo, cdo-i. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdo1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.70Å R-factor: 0.178 R-free: 0.215

Authors:

S.Ye,X.Wu,L.Wei,D.Tang,P.Sun,Z.Rao

Key ref:

S.Ye et al. (2007). An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. J Biol Chem, 282, 3391-3402. PubMed id: 17135237 DOI: 10.1074/jbc.M609337200

Date:

12-Sep-06 Release date: 05-Dec-06

Protein chain

Q16878  (CDO1_HUMAN) -  Cysteine dioxygenase type 1 from Homo sapiens

Seq: 200 a.a.

Struc: 185 a.a.

Enzyme reactions

• Enzyme class: E.C.1.13.11.20 - cysteine dioxygenase.
• Reaction: L-cysteine + O2 = 3-sulfino-L-alanine + H⁺

L-cysteine (Bound ligand (Het Group name = CYS) corresponds exactly) + O2 = 3-sulfino-L-alanine + H(+)

• Cofactor: Fe(2+); NADH or NADPH

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

reference

DOI no: 10.1074/jbc.M609337200

J Biol Chem 282:3391-3402 (2007)

PubMed id: 17135237

An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor.

S.Ye, X.Wu, L.Wei, D.Tang, P.Sun, M.Bartlam, Z.Rao.

ABSTRACT

Cysteine dioxygenase is a non-heme mononuclear iron metalloenzyme that catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen. This irreversible oxidative catabolism of cysteine initiates several important metabolic pathways related to diverse sulfurate compounds. Cysteine dioxygenase is therefore very important for maintaining the proper hepatic concentration of intracellular free cysteine. Mechanisms for mouse and rat cysteine dioxygenases have recently been reported based on their crystal structures in the absence of substrates, although there is still a lack of direct evidence. Here we report the first crystal structure of human cysteine dioxygenase in complex with its substrate L-cysteine to 2.7A, together with enzymatic activity and metal content assays of several single point mutants. Our results provide an insight into a new mechanism of cysteine thiol dioxygenation catalyzed by cysteine dioxygenase, which is tightly associated with a thioether-bonded tyrosine-cysteine cofactor involving Tyr-157 and Cys-93. This cross-linked protein-derived cofactor plays several key roles different from those in galactose oxidase. This report provides a new potential target for therapy of diseases related to human cysteine dioxygenase, including neurodegenerative and autoimmune diseases.

Selected figure(s)

Figure 2.
FIGURE 2. Overall crystal structure of human CDO in complex with the cysteine substrate. A, a stereo view ribbon representation with secondary structure assignments. The -barrel is made up of two antiparallel -sheets colored yellow and brown and a mixed -sheet colored red. Helices are colored in cyan, and the ferrous ion is colored turquoise. The cysteine substrate is shown in ball-and-stick representation. B, electrostatic potential of the human CDO crystal structure, calculated using PyMOL (DeLano Scientific, San Carlos, CA). Negatively charged regions are colored in red, positively charged regions are blue, and neutral regions are white. A hole from the surface to the active center is very clear, through which the substrate cysteine can be seen. C, superposition of human, mouse, and rat CDO. Human CDO is colored in red, mouse CDO in green, and rat CDO in blue. Non-conserved residues are highlighted as sticks. Among these three CDOs, the central region around the active site is highly conserved both in primary sequence and in three-dimensional conformation.

Figure 7.
FIGURE 7. Catalytic mechanism of human CDO. See the text for detailed discussion.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 3391-3402) copyright 2007.

Figures were selected by an automated process.