PDBsum entry 1u8v

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Lyase, isomerase PDB id
Protein chains
490 a.a. *
SF4 ×4
FAD ×4
Waters ×2336
* Residue conservation analysis
PDB id:
Name: Lyase, isomerase
Title: Crystal structure of 4-hydroxybutyryl-coa dehydratase from clostridium aminobutyricum: radical catalysis involving a [4fe-4s] cluster and flavin
Structure: Gamma-aminobutyrate metabolism dehydratase/isomerase. Chain: a, b, c, d. Ec: 4.2.-.-,
Source: Clostridium aminobutyricum. Organism_taxid: 33953
Biol. unit: Tetramer (from PQS)
1.60Å     R-factor:   0.163     R-free:   0.212
Authors: B.M.Martins,H.Dobbek,I.Cinkaya,W.Buckel,A.Messerschmidt
Key ref:
B.M.Martins et al. (2004). Crystal structure of 4-hydroxybutyryl-CoA dehydratase: radical catalysis involving a [4Fe-4S] cluster and flavin. Proc Natl Acad Sci U S A, 101, 15645-15649. PubMed id: 15496473 DOI: 10.1073/pnas.0403952101
07-Aug-04     Release date:   21-Dec-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P55792  (HDVD_CLOAM) -  4-hydroxybutyryl-CoA dehydratase/vinylacetyl-CoA-Delta-isomerase
490 a.a.
490 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - 4-hydroxybutanoyl-CoA dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-hydroxybutanoyl-CoA = but-3-enoyl-CoA + H2O
Bound ligand (Het Group name = FAD)
matches with 45.00% similarity
= but-3-enoyl-CoA
+ H(2)O
      Cofactor: FAD; Iron-sulfur
   Enzyme class 2: E.C.  - Vinylacetyl-CoA Delta-isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Vinylacetyl-CoA = (E)-but-2-enoyl-CoA
= (E)-but-2-enoyl-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!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     11 terms  


DOI no: 10.1073/pnas.0403952101 Proc Natl Acad Sci U S A 101:15645-15649 (2004)
PubMed id: 15496473  
Crystal structure of 4-hydroxybutyryl-CoA dehydratase: radical catalysis involving a [4Fe-4S] cluster and flavin.
B.M.Martins, H.Dobbek, I.Cinkaya, W.Buckel, A.Messerschmidt.
Dehydratases catalyze the breakage of a carbon-oxygen bond leading to unsaturated products via the elimination of water. The 1.6-A resolution crystal structure of 4-hydroxybutyryl-CoA dehydratase from the gamma-aminobutyrate-fermenting Clostridium aminobutyricum represents a new class of dehydratases with an unprecedented active site architecture. A [4Fe-4S](2+) cluster, coordinated by three cysteine and one histidine residues, is located 7 A from the Re-side of a flavin adenine dinucleotide (FAD) moiety. The structure provides insight into the function of these ubiquitous prosthetic groups in the chemically nonfacile, radical-mediated dehydration of 4-hydroxybutyryl-CoA. The substrate can be bound between the [4Fe-4S](2+) cluster and the FAD with both cofactors contributing to its radical activation and catalytic conversion. Our results raise interesting questions regarding the mechanism of acyl-CoA dehydrogenases, which are involved in fatty acid oxidation, and address the divergent evolution of the ancestral common gene.
  Selected figure(s)  
Figure 1.
Fig. 1. Crystal structure. (A) Surface representation of the 4-BUDH homotetramer. Each monomer's surface is individually colored, and the FAD's surface is shown in cyan. (B) Secondary structure topology of the monomer with the N-terminal domain (residues Met-1 to Leu-143) shown in red, the middle domain (residues Ile-144 to Gln-276) shown in green, and the C-terminal domain (residues Glu-277 to Lys-490) shown in blue. The [4Fe-4S]2+ cluster is shown as ball-and-sticks with Fe and S atoms shown in red and yellow, respectively. The FAD is displayed in sticks and shown in cyan. The N and C termini of the polypeptide chain are marked. (C) Example of the well defined electron density for the refined model (2 F[o] - F[c] electron density map contoured at 1.0 and shown in gray). Atom color code for protein residues and FAD is cream for carbon, red for oxygen, blue for nitrogen, and yellow for sulfur. Color code for the [4Fe-4S]2+ cluster is as in B. This figure and Fig. 2 were prepared with PYMOL (44).
Figure 3.
Fig. 3. Proposed radical-mediated mechanism of 4-BUDH. The catalytic base His-292 abstracts the C2-proR-hydrogen and protonates the C4 position of the last reaction intermediate, dienolate. The C3-proS-hydrogen is abstracted by the semiquinone anion and, together with the hydroxyl group, forms the byproduct water molecule.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21226770 M.Gu, and J.A.Imlay (2011).
The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide.
  Mol Microbiol, 79, 1136-1150.  
19915006 B.N.Webb, J.W.Ballinger, E.Kim, S.M.Belchik, K.S.Lam, B.Youn, M.S.Nissen, L.Xun, and C.Kang (2010).
Characterization of chlorophenol 4-monooxygenase (TftD) and NADH:FAD oxidoreductase (TftC) of Burkholderia cepacia AC1100.
  J Biol Chem, 285, 2014-2027.
PDB codes: 3hwc 3k86 3k87 3k88
20453874 I.A.Berg, D.Kockelkorn, W.H.Ramos-Vera, R.F.Say, J.Zarzycki, M.Hügler, B.E.Alber, and G.Fuchs (2010).
Autotrophic carbon fixation in archaea.
  Nat Rev Microbiol, 8, 447-460.  
20149100 S.Korshunov, and J.A.Imlay (2010).
Two sources of endogenous hydrogen peroxide in Escherichia coli.
  Mol Microbiol, 75, 1389-1401.  
20693323 W.H.Ramos-Vera, V.Labonté, M.Weiss, J.Pauly, and G.Fuchs (2010).
Regulation of autotrophic CO2 fixation in the archaeon Thermoproteus neutrophilus.
  J Bacteriol, 192, 5329-5340.  
19411323 W.H.Ramos-Vera, I.A.Berg, and G.Fuchs (2009).
Autotrophic carbon dioxide assimilation in Thermoproteales revisited.
  J Bacteriol, 191, 4286-4297.  
18655062 A.Liavonchanka, and I.Feussner (2008).
Biochemistry of PUFA double bond isomerases producing conjugated linoleic acid.
  Chembiochem, 9, 1867-1872.  
18511565 H.Huber, M.Gallenberger, U.Jahn, E.Eylert, I.A.Berg, D.Kockelkorn, W.Eisenreich, and G.Fuchs (2008).
A dicarboxylate/4-hydroxybutyrate autotrophic carbon assimilation cycle in the hyperthermophilic Archaeum Ignicoccus hospitalis.
  Proc Natl Acad Sci U S A, 105, 7851-7856.  
17898896 A.Marquet, B.T.Bui, A.G.Smith, and M.J.Warren (2007).
Iron-sulfur proteins as initiators of radical chemistry.
  Nat Prod Rep, 24, 1027-1040.  
17640900 G.Yakovlev, T.Reda, and J.Hirst (2007).
Reevaluating the relationship between EPR spectra and enzyme structure for the iron sulfur clusters in NADH:quinone oxidoreductase.
  Proc Natl Acad Sci U S A, 104, 12720-12725.  
18079405 I.A.Berg, D.Kockelkorn, W.Buckel, and G.Fuchs (2007).
A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea.
  Science, 318, 1782-1786.  
16430685 J.A.Imlay (2006).
Iron-sulphur clusters and the problem with oxygen.
  Mol Microbiol, 59, 1073-1082.  
17010373 J.Chartron, K.S.Carroll, C.Shiau, H.Gao, J.A.Leary, C.R.Bertozzi, and C.D.Stout (2006).
Substrate recognition, protein dynamics, and iron-sulfur cluster in Pseudomonas aeruginosa adenosine 5'-phosphosulfate reductase.
  J Mol Biol, 364, 152-169.
PDB code: 2goy
17070680 L.De Colibus, and A.Mattevi (2006).
New frontiers in structural flavoenzymology.
  Curr Opin Struct Biol, 16, 722-728.  
16640564 M.Mack, U.Schniegler-Mattox, V.Peters, G.F.Hoffmann, M.Liesert, W.Buckel, and J.Zschocke (2006).
Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolism.
  FEBS J, 273, 2012-2022.  
16704345 W.Buckel, and B.T.Golding (2006).
Radical enzymes in anaerobes.
  Annu Rev Microbiol, 60, 27-49.  
16218867 W.Buckel, B.M.Martins, A.Messerschmidt, and B.T.Golding (2005).
Radical-mediated dehydration reactions in anaerobic bacteria.
  Biol Chem, 386, 951-959.  
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 codes are shown on the right.