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PDBsum entry 3e08

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
3e08
Jmol
Contents
Protein chains
(+ 2 more) 280 a.a. *
Ligands
TRP ×16
HEM ×8
Waters ×1955
* Residue conservation analysis
PDB id:
3e08
Name: Oxidoreductase
Title: H55s mutant xanthomonas campestris tryptophan 2,3- dioxygenase
Structure: Tryptophan 2,3-dioxygenase. Chain: a, b, c, d, e, f, g, h. Engineered: yes. Mutation: yes
Source: Xanthomonas campestris pv. Campestris. Organism_taxid: 340. Gene: xccb100_0466. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.178     R-free:   0.216
Authors: C.G.Mowat,L.P.Campbell
Key ref: S.J.Thackray et al. (2008). Histidine 55 of tryptophan 2,3-dioxygenase is not an active site base but regulates catalysis by controlling substrate binding. Biochemistry, 47, 10677-10684. PubMed id: 18783250 DOI: 10.1021/bi801202a
Date:
31-Jul-08     Release date:   30-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8PDA8  (T23O_XANCP) -  Tryptophan 2,3-dioxygenase
Seq:
Struc:
298 a.a.
280 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
Bound ligand (Het Group name = TRP)
corresponds exactly
+ O(2)
= N-formyl-L-kynurenine
      Cofactor: Heme
Heme
Bound ligand (Het Group name = HEM) matches with 95.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     oxidoreductase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi801202a Biochemistry 47:10677-10684 (2008)
PubMed id: 18783250  
 
 
Histidine 55 of tryptophan 2,3-dioxygenase is not an active site base but regulates catalysis by controlling substrate binding.
S.J.Thackray, C.Bruckmann, J.L.Anderson, L.P.Campbell, R.Xiao, L.Zhao, C.G.Mowat, F.Forouhar, L.Tong, S.K.Chapman.
 
  ABSTRACT  
 
Tryptophan 2,3-dioxygenase (TDO) from Xanthomonas campestris is a highly specific heme-containing enzyme from a small family of homologous enzymes, which includes indoleamine 2,3-dioxygenase (IDO). The structure of wild type (WT TDO) in the catalytically active, ferrous (Fe (2+)) form and in complex with its substrate l-tryptophan ( l-Trp) was recently reported [Forouhar et al. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 473-478] and revealed that histidine 55 hydrogen bonds to l-Trp, precisely positioning it in the active site and implicating it as a possible active site base. In this study the substitution of the active site residue histidine 55 by alanine and serine (H55A and H55S) provides insight into the molecular mechanism used by the enzyme to control substrate binding. We report the crystal structure of the H55A and H55S mutant forms at 2.15 and 1.90 A resolution, respectively, in binary complexes with l-Trp. These structural data, in conjunction with potentiometric and kinetic studies on both mutants, reveal that histidine 55 is not essential for turnover but greatly disfavors the mechanistically unproductive binding of l-Trp to the oxidized enzyme allowing control of catalysis. This is demonstrated by the difference in the K d values for l-Trp binding to the two oxidation states of wild-type TDO (3.8 mM oxidized, 4.1 microM reduced), H55A TDO (11.8 microM oxidized, 3.7 microM reduced), and H55S TDO (18.4 microM oxidized, 5.3 microM reduced).
 

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.  
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.  
19218188 E.Fukumura, H.Sugimoto, Y.Misumi, T.Ogura, and Y.Shiro (2009).
Cooperative binding of L-trp to human tryptophan 2,3-dioxygenase: resonance Raman spectroscopic analysis.
  J Biochem, 145, 505-515.  
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.