PDBsum entry 1wdm

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protein ligands metals Protein-protein interface(s) links
Lyase,oxidoreductase/transferase PDB id
Protein chains
707 a.a. *
390 a.a. *
ACO ×3
NAD ×2
* Residue conservation analysis
PDB id:
Name: Lyase,oxidoreductase/transferase
Title: Fatty acid beta-oxidation multienzyme complex from pseudomonas fragi, form i (native3)
Structure: Fatty oxidation complex alpha subunit. Chain: a, b. Synonym: fatty acid beta-oxidation multienzyme complex, alpha subunit. Ec:,,, Engineered: yes. 3-ketoacyl-coa thiolase. Chain: c, d. Synonym: fatty acid beta-oxidation multienzyme complex,
Source: Pseudomonas fragi. Organism_taxid: 296. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
3.80Å     R-factor:   0.214     R-free:   0.262
Authors: M.Ishikawa,D.Tsuchiya,T.Oyama,Y.Tsunaka,K.Morikawa
Key ref:
M.Ishikawa et al. (2004). Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex. EMBO J, 23, 2745-2754. PubMed id: 15229654 DOI: 10.1038/sj.emboj.7600298
17-May-04     Release date:   27-Jul-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P28793  (FADB_PSEFR) -  Fatty acid oxidation complex subunit alpha
715 a.a.
707 a.a.
Protein chains
Pfam   ArchSchema ?
P28790  (FADA_PSEFR) -  3-ketoacyl-CoA thiolase
391 a.a.
390 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, B: E.C.  - 3-hydroxyacyl-CoA dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH
Bound ligand (Het Group name = ACO)
matches with 94.00% similarity
Bound ligand (Het Group name = NAD)
corresponds exactly
= 3-oxoacyl-CoA
   Enzyme class 2: Chains A, B: E.C.  - Enoyl-CoA hydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O
Bound ligand (Het Group name = ACO)
matches with 94.00% similarity
= trans-2(or 3)-enoyl-CoA
+ H(2)O
   Enzyme class 3: Chains A, B: E.C.  - 3-hydroxybutyryl-CoA epimerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-3-hydroxybutanoyl-CoA = (R)-3-hydroxybutanoyl-CoA
Bound ligand (Het Group name = ACO)
matches with 94.00% similarity
= (R)-3-hydroxybutanoyl-CoA
   Enzyme class 4: Chains A, B: E.C.  - Dodecenoyl-CoA isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3Z)-dodec-3-enoyl-CoA = (2E)-dodec-2-enoyl-CoA
Bound ligand (Het Group name = ACO)
matches with 83.00% similarity
= (2E)-dodec-2-enoyl-CoA
   Enzyme class 5: Chains C, D: E.C.  - Acetyl-CoA C-acyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA
Bound ligand (Het Group name = ACO)
corresponds exactly
= CoA
+ 3-oxoacyl-CoA
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     fatty acid beta-oxidation multienzyme complex   2 terms 
  Biological process     metabolic process   7 terms 
  Biochemical function     catalytic activity     15 terms  


DOI no: 10.1038/sj.emboj.7600298 EMBO J 23:2745-2754 (2004)
PubMed id: 15229654  
Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex.
M.Ishikawa, D.Tsuchiya, T.Oyama, Y.Tsunaka, K.Morikawa.
The atomic view of the active site coupling termed channelling is a major subject in molecular biology. We have determined two distinct crystal structures of the bacterial multienzyme complex that catalyzes the last three sequential reactions in the fatty acid beta-oxidation cycle. The alpha2beta2 heterotetrameric structure shows the uneven ring architecture, where all the catalytic centers of 2-enoyl-CoA hydratase (ECH), L-3-hydroxyacyl-CoA dehydrogenase (HACD) and 3-ketoacyl-CoA thiolase (KACT) face a large inner solvent region. The substrate, anchored through the 3'-phosphate ADP moiety, allows the fatty acid tail to pivot from the ECH to HACD active sites, and finally to the KACT active site. Coupling with striking domain rearrangements, the incorporation of the tail into the KACT cavity and the relocation of 3'-phosphate ADP bring the reactive C2-C3 bond to the correct position for cleavage. The alpha-helical linker specific for the multienzyme contributes to the pivoting center formation and the substrate transfer through its deformation. This channelling mechanism could be applied to other beta-oxidation multienzymes, as revealed from the homology model of the human mitochondrial trifunctional enzyme complex.
  Selected figure(s)  
Figure 2.
Figure 2 Active sites of three FOM components. Stereo diagrams show catalytic and hydrophobic residues around ligands in Form I. (A) Two C[8]E[5] molecules bound to each ECH of the dimer ( 1 and 2) in different modes, 'inside' (clear gray) and 'outside' (faint gray). The alkyl groups of two C[8]E[5] molecules are trapped with hydrophobic residues. Some parts of main chains (light brown) represent identical portions to rECH (Engel et al, 1996). (B) Ac-CoA and NAD^+ molecules bound to HACD in the Native3 crystal. The acetyl group of Ac-CoA points into the hydrophobic tunnel. (C) Ac-CoA molecules bound to the two KACT subunits. In Form II, the interaction of Arg369 with Val134 causes the 1 elevation (arrow) of the loop containing Val134 and Pro136 (cyan), and the subsequent rotation of the Trp70: 2 side chain (cyan).
Figure 5.
Figure 5 Homology model of the human TFE complex. (A) The symmetric TFE architecture, with the mutation sites (red spheres) relevant to various genetic diseases (Ibdah et al, 1998; Eaton et al, 2000). The arrowheads denote the HACD active sites. The inset indicates Val282, located in the interface between ECH in the -subunit and KACT in the -subunit. The insertion specific for TFE is depicted by dotted lines with asterisks. (B) Electrostatic surface representation showing the biased distribution of positive charges around the central solvent region.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 2745-2754) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21320074 T.J.Haataja, M.K.Koski, J.K.Hiltunen, and T.Glumoff (2011).
Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics.
  Biochem J, 435, 771-781.
PDB code: 3oml
20957111 la Fuente (2010).
Quantitative analysis of cellular metabolic dissipative, self-organized structures.
  Int J Mol Sci, 11, 3540-3599.  
20051520 R.Matsunaga-Udagawa, Y.Fujita, S.Yoshiki, K.Terai, Y.Kamioka, E.Kiyokawa, K.Yugi, K.Aoki, and M.Matsuda (2010).
The scaffold protein Shoc2/SUR-8 accelerates the interaction of Ras and Raf.
  J Biol Chem, 285, 7818-7826.  
19952418 M.Sugitani, R.Abe, N.Ikarashi, K.Ito, H.Muratake, K.Shudo, and K.Sugiyama (2009).
Disposition of a new tamibarotene prodrug in mice.
  Biol Pharm Bull, 32, 1997-2001.  
18476872 J.B.van Beilen, and Y.Poirier (2008).
Production of renewable polymers from crop plants.
  Plant J, 54, 684-701.  
18725290 R.J.Conrado, J.D.Varner, and M.P.DeLisa (2008).
Engineering the spatial organization of metabolic enzymes: mimicking nature's synergy.
  Curr Opin Biotechnol, 19, 492-499.  
17431175 S.Jenni, M.Leibundgut, D.Boehringer, C.Frick, B.Mikolásek, and N.Ban (2007).
Structure of fungal fatty acid synthase and implications for iterative substrate shuttling.
  Science, 316, 254-261.
PDB codes: 2uv9 2uva 2uvb 2uvc
17928301 T.W.Geders, L.Gu, J.C.Mowers, H.Liu, W.H.Gerwick, K.Håkansson, D.H.Sherman, and J.L.Smith (2007).
Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain beta-branching.
  J Biol Chem, 282, 35954-35963.
PDB codes: 2q2x 2q34 2q35
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. Where a reference describes a PDB structure, the PDB code is shown on the right.