PDBsum entry 2b5h

Oxidoreductase

PDB id: 2b5h

Contents

Protein chain

186 a.a. *

Metals

_FE

Waters ×326

* Residue conservation analysis

PDB id:

2b5h

Name:

Oxidoreductase

Title:

1.5 a resolution crystal structure of recombinant r. Norvegicus cysteine dioxygenase

Structure:

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

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: cdo1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.50Å R-factor: 0.182 R-free: 0.208

Authors:

C.R.Simmons,Q.Liu,Q.Huang,Q.Hao,T.P.Begley,P.A.Karplus,M.H.Stipanuk

Key ref:

C.R.Simmons et al. (2006). Crystal structure of mammalian cysteine dioxygenase. A novel mononuclear iron center for cysteine thiol oxidation. J Biol Chem, 281, 18723-18733. PubMed id: 16611640 DOI: 10.1074/jbc.M601555200

Date:

28-Sep-05 Release date: 11-Apr-06

Protein chain

P21816  (CDO1_RAT) -  Cysteine dioxygenase type 1 from Rattus norvegicus

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-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.M601555200

J Biol Chem 281:18723-18733 (2006)

PubMed id: 16611640

Crystal structure of mammalian cysteine dioxygenase. A novel mononuclear iron center for cysteine thiol oxidation.

C.R.Simmons, Q.Liu, Q.Huang, Q.Hao, T.P.Begley, P.A.Karplus, M.H.Stipanuk.

ABSTRACT

Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the oxidation of cysteine with molecular oxygen to form cysteine sulfinate. This reaction commits cysteine to either catabolism to sulfate and pyruvate or the taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin superfamily of proteins. The crystal structure of recombinant rat cysteine dioxygenase has been determined to 1.5-A resolution, and these results confirm the canonical cupin beta-sandwich fold and the rare cysteinyltyrosine intramolecular cross-link (between Cys(93) and Tyr(157)) seen in the recently reported murine cysteine dioxygenase structure. In contrast to the catalytically inactive mononuclear Ni(II) metallocenter present in the murine structure, crystallization of a catalytically competent preparation of rat cysteine dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center involving three histidines (His(86), His(88), and His(140)) and a water molecule. Attempts to acquire a structure with bound ligand using either cocrystallization or soaking crystals with cysteine revealed the formation of a mixed disulfide involving Cys(164) near the active site, which may explain previously observed substrate inhibition. This work provides a framework for understanding the molecular mechanisms involved in thiol dioxygenation and sets the stage for exploration of the chemistry of both the novel mononuclear iron center and the catalytic role of the cysteinyl-tyrosine linkage.

Selected figure(s)

Figure 1.
FIGURE 1. Electron density evidence for key features of the CDO active site. 2F[o] - F[c] electron density is shown contoured at 1.6 . Stick representations of select protein residues, including the Cys-Tyr linkage, are shown with iron (orange sphere) and active site waters (red spheres). All structural figures within this report were prepared using PyMOL (62).

Figure 8.
FIGURE 8. Mechanistic proposals for CDO. Scheme A, mechanistic proposal for the catalytic cycle of cysteine oxidation. The letter B in this Scheme A indicates a putative active site base. Scheme B, mechanistic proposal for the single turnover event generating the cysteinyl-tyrosine thioether cross-link. Each mechanism is discussed in the text (see "Discussion").

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 18723-18733) copyright 2006.

Figures were selected by an automated process.