PDBsum entry 2nox

Oxidoreductase

PDB id

2nox

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Contents

			Protein chains

					(+ 10 more) 261 a.a. *

			Ligands

					HEM ×16

			Waters ×1543

* Residue conservation analysis

PDB id:

2nox

Links

Name:

Oxidoreductase

Title:

Crystal structure of tryptophan 2,3-dioxygenase from ralstonia metallidurans

Structure:

Tryptophan 2,3-dioxygenase. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p. Ec: 1.13.11.11

Source:

Cupriavidus metallidurans. Organism_taxid: 119219

Resolution:

2.40Å

R-factor:

0.210

R-free:

0.270

Authors:

Y.Zhang,S.A.Kang,T.Mukherjee,S.Bale,B.R.Crane,T.P.Begley,S.E.Ealick

Key ref:

Y.Zhang et al. (2007). Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis. Biochemistry, 46, 145-155. PubMed id: 17198384 DOI: 10.1021/bi0620095

Date:

26-Oct-06

Release date:

19-Dec-06

PROCHECK

	Headers

	References

Protein chains

Q1LK00 (T23O_CUPMC) - Tryptophan 2,3-dioxygenase from Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34)

Seq: Struc:					299 a.a. 261 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.1.13.11.11 - tryptophan 2,3-dioxygenase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Tryptophan Catabolism

Reaction:

L-tryptophan + O2 = N-formyl-L-kynurenine

L-tryptophan	+	O2	=	N-formyl-L-kynurenine

Cofactor:

Heme

Heme
Bound ligand (Het Group name = HEM) matches with 95.45% similarity

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

reference

DOI no: 10.1021/bi0620095	Biochemistry 46:145-155 (2007)
PubMed id: 17198384

Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis.
Y.Zhang, S.A.Kang, T.Mukherjee, S.Bale, B.R.Crane, T.P.Begley, S.E.Ealick.

ABSTRACT

The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans was determined at 2.4 A. TDO catalyzes the irreversible oxidation of l-tryptophan to N-formyl kynurenine, which is the initial step in tryptophan catabolism. TDO is a heme-containing enzyme and is highly specific for its substrate l-tryptophan. The structure is a tetramer with a heme cofactor bound at each active site. The monomeric fold, as well as the heme binding site, is similar to that of the large domain of indoleamine 2,3-dioxygenase, an enzyme that catalyzes the same reaction except with a broader substrate tolerance. Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrate analogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20361220

L.Capece, A.Lewis-Ballester, D.Batabyal, N.Di Russo, S.R.Yeh, D.A.Estrin, and M.A.Marti (2010).
The first step of the dioxygenation reaction carried out by tryptophan dioxygenase and indoleamine 2,3-dioxygenase as revealed by quantum mechanical/molecular mechanical studies.

J Biol Inorg Chem, 15, 811-823.

20715188

L.Capece, M.Arrar, A.E.Roitberg, S.R.Yeh, M.A.Marti, and D.A.Estrin (2010).
Substrate stereo-specificity in tryptophan dioxygenase and indoleamine 2,3-dioxygenase.

Proteins, 78, 2961-2972.

20353179

R.M.Davydov, N.Chauhan, S.J.Thackray, J.L.Anderson, N.D.Papadopoulou, C.G.Mowat, S.K.Chapman, E.L.Raven, and B.M.Hoffman (2010).
Probing the ternary complexes of indoleamine and tryptophan 2,3-dioxygenases by cryoreduction EPR and ENDOR spectroscopy.

J Am Chem Soc, 132, 5494-5500.

20636821

U.Grohmann, and V.Bronte (2010).
Control of immune response by amino acid metabolism.

Immunol Rev, 236, 243-264.

19805032

A.Lewis-Ballester, D.Batabyal, T.Egawa, C.Lu, Y.Lin, M.A.Marti, L.Capece, D.A.Estrin, and S.R.Yeh (2009).
Evidence for a ferryl intermediate in a heme-based dioxygenase.

Proc Natl Acad Sci U S A, 106, 17371-17376.

18612775

A.Macchiarulo, E.Camaioni, R.Nuti, and R.Pellicciari (2009).
Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease.

Amino Acids, 37, 219-229.

19461669

S.Löb, A.Königsrainer, H.G.Rammensee, G.Opelz, and P.Terness (2009).
Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees?

Nat Rev Cancer, 9, 445-452.

18493661

A.Sheoran, A.King, A.Velasco, J.M.Pero, and S.Garneau-Tsodikova (2008).
Characterization of TioF, a tryptophan 2,3-dioxygenase involved in 3-hydroxyquinaldic acid formation during thiocoraline biosynthesis.

Mol Biosyst, 4, 622-628.

18515349

M.von Grotthuss, D.Plewczynski, G.Vriend, and L.Rychlewski (2008).
3D-Fun: predicting enzyme function from structure.

Nucleic Acids Res, 36, W303-W307.

19021508

S.J.Thackray, C.G.Mowat, and S.K.Chapman (2008).
Exploring the mechanism of tryptophan 2,3-dioxygenase.

Biochem Soc Trans, 36, 1120-1123.

18026683

H.J.Yuasa, M.Takubo, A.Takahashi, T.Hasegawa, H.Noma, and T.Suzuki (2007).
Evolution of vertebrate indoleamine 2,3-dioxygenases.

J Mol Evol, 65, 705-714.

17535808

S.R.Thomas, A.C.Terentis, H.Cai, O.Takikawa, A.Levina, P.A.Lay, M.Freewan, and R.Stocker (2007).
Post-translational regulation of human indoleamine 2,3-dioxygenase activity by nitric oxide.

J Biol Chem, 282, 23778-23787.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.