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PDBsum entry 1dub

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1dub
Jmol
Contents
Protein chains
(+ 0 more) 260 a.a. *
Ligands
CAA ×5
Waters ×595
* Residue conservation analysis
PDB id:
1dub
Name: Lyase
Title: 2-enoyl-coa hydratase, data collected at 100 k, ph 6.5
Structure: 2-enoyl-coa hydratase. Chain: a, b, c, d, e, f. Synonym: crotonase, enoyl-coa hydratase 1. Ec: 4.2.1.17
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver
Biol. unit: Homo-Hexamer (from PDB file)
Resolution:
2.50Å     R-factor:   0.209     R-free:   0.265
Authors: R.K.Wierenga,C.K.Engel
Key ref: C.K.Engel et al. (1996). Crystal structure of enoyl-coenzyme A (CoA) hydratase at 2.5 angstroms resolution: a spiral fold defines the CoA-binding pocket. EMBO J, 15, 5135-5145. PubMed id: 8895557
Date:
10-Jun-96     Release date:   07-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P14604  (ECHM_RAT) -  Enoyl-CoA hydratase, mitochondrial
Seq:
Struc:
290 a.a.
260 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.17  - Enoyl-CoA hydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O
(3S)-3-hydroxyacyl-CoA
Bound ligand (Het Group name = CAA)
matches with 96.00% similarity
= trans-2(or 3)-enoyl-CoA
+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Key reference    
 
 
EMBO J 15:5135-5145 (1996)
PubMed id: 8895557  
 
 
Crystal structure of enoyl-coenzyme A (CoA) hydratase at 2.5 angstroms resolution: a spiral fold defines the CoA-binding pocket.
C.K.Engel, M.Mathieu, J.P.Zeelen, J.K.Hiltunen, R.K.Wierenga.
 
  ABSTRACT  
 
The crystal structure of rat liver mitochondrial enoyl-coenzyme A (CoA) hydratase complexed with the potent inhibitor acetoacetyl-CoA has been refined at 2.5 angstroms resolution. This enzyme catalyses the reversible addition of water to alpha,beta-unsaturated enoyl-CoA thioesters, with nearly diffusion-controlled reaction rates for the best substrates. Enoyl-CoA hydratase is a hexamer of six identical subunits of 161 kDa molecular mass for the complex. The hexamer is a dimer of trimers. The monomer is folded into a right-handed spiral of four turns, followed by two small domains which are involved in trimerization. Each turn of the spiral consists of two beta-strands and an alpha-helix. The mechanism for the hydratase/dehydratase reaction follows a syn-stereochemistry, a preference that is opposite to the nonenzymatic reaction. The active-site architecture agrees with this stereochemistry. It confirms the importance of Glu164 as the catalytic acid for providing the alpha-proton during the hydratase reaction. It also shows the importance of Glu144 as the catalytic base for the activation of a water molecule in the hydratase reaction. The comparison of an unliganded and a liganded active site within the same crystal form shows a water molecule in the unliganded subunit. This water molecule is bound between the two catalytic glutamates and could serve as the activated water during catalysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308811 I.Pápai, A.Hamza, P.M.Pihko, and R.K.Wierenga (2011).
Stereoelectronic requirements for optimal hydrogen-bond-catalyzed enolization.
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21243161 J.Jin, and U.Hanefeld (2011).
The selective addition of water to C=C bonds; enzymes are the best chemists.
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Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association.
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19369256 J.Bains, R.Leon, and M.J.Boulanger (2009).
Structural and Biophysical Characterization of BoxC from Burkholderia xenovorans LB400: A NOVEL RING-CLEAVING ENZYME IN THE CROTONASE SUPERFAMILY.
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PDB code: 2w3p
18831052 K.Kurimoto, K.Kuwasako, A.M.Sandercock, S.Unzai, C.V.Robinson, Y.Muto, and S.Yokoyama (2009).
AU-rich RNA-binding induces changes in the quaternary structure of AUH.
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PDB codes: 2zqq 2zqr
19562746 T.Lendrihas, J.Zhang, G.A.Hunter, and G.C.Ferreira (2009).
Arg-85 and Thr-430 in murine 5-aminolevulinate synthase coordinate acyl-CoA-binding and contribute to substrate specificity.
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17650509 A.Faye, C.Esnous, N.T.Price, M.A.Onfray, J.Girard, and C.Prip-Buus (2007).
Rat liver carnitine palmitoyltransferase 1 forms an oligomeric complex within the outer mitochondrial membrane.
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Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle - structure/function study of Xenopus IRBP.
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Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain beta-branching.
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PDB codes: 2q2x 2q34 2q35
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Interphotoreceptor retinoid-binding protein gene structure in tetrapods and teleost fish.
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16482430 M.Mack, M.Liesert, J.Zschocke, V.Peters, D.Linder, and W.Buckel (2006).
3-Methylglutaconyl-CoA hydratase from Acinetobacter sp.
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17139085 P.M.Leonard, A.M.Brzozowski, A.Lebedev, C.M.Marshall, D.J.Smith, C.S.Verma, N.J.Walton, and G.Grogan (2006).
The 1.8 A resolution structure of hydroxycinnamoyl-coenzyme A hydratase-lyase (HCHL) from Pseudomonas fluorescens, an enzyme that catalyses the transformation of feruloyl-coenzyme A to vanillin.
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PDB code: 2j5i
15731894 C.Engemann, T.Elssner, S.Pfeifer, C.Krumbholz, T.Maier, and H.P.Kleber (2005).
Identification and functional characterisation of genes and corresponding enzymes involved in carnitine metabolism of Proteus sp.
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16131752 J.M.Johnston, V.L.Arcus, and E.N.Baker (2005).
Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms.
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16096274 M.C.Sleeman, J.L.Sorensen, E.T.Batchelar, M.A.McDonough, and C.J.Schofield (2005).
Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis.
  J Biol Chem, 280, 34956-34965.
PDB codes: 2a7k 2a81
15883186 P.A.Hubbard, W.Yu, H.Schulz, and J.J.Kim (2005).
Domain swapping in the low-similarity isomerase/hydratase superfamily: the crystal structure of rat mitochondrial Delta3, Delta2-enoyl-CoA isomerase.
  Protein Sci, 14, 1545-1555.
PDB code: 1xx4
15229654 M.Ishikawa, D.Tsuchiya, T.Oyama, Y.Tsunaka, and K.Morikawa (2004).
Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex.
  EMBO J, 23, 2745-2754.
PDB codes: 1wdk 1wdl 1wdm
15138275 P.M.Leonard, and G.Grogan (2004).
Structure of 6-oxo camphor hydrolase H122A mutant bound to its natural product, (2S,4S)-alpha-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog.
  J Biol Chem, 279, 31312-31317.
PDB code: 1szo
12947414 C.Caron, C.Pivot-Pajot, L.A.van Grunsven, E.Col, C.Lestrat, S.Rousseaux, and S.Khochbin (2003).
Cdyl: a new transcriptional co-repressor.
  EMBO Rep, 4, 877-882.  
12393860 C.V.Smith, C.C.Huang, A.Miczak, D.G.Russell, J.C.Sacchettini, and K.Höner zu Bentrup (2003).
Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis.
  J Biol Chem, 278, 1735-1743.
PDB codes: 1n8i 1n8w
12663926 H.Zhang, Z.Yang, Y.Shen, and L.Tong (2003).
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase.
  Science, 299, 2064-2067.
PDB codes: 1od2 1od4
12909628 J.J.Truglio, K.Theis, Y.Feng, R.Gajda, C.Machutta, P.J.Tonge, and C.Kisker (2003).
Crystal structure of Mycobacterium tuberculosis MenB, a key enzyme in vitamin K2 biosynthesis.
  J Biol Chem, 278, 42352-42360.
PDB codes: 1q51 1q52
12697341 J.K.Hiltunen, A.M.Mursula, H.Rottensteiner, R.K.Wierenga, A.J.Kastaniotis, and A.Gurvitz (2003).
The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae.
  FEMS Microbiol Rev, 27, 35-64.  
12421807 J.L.Whittingham, J.P.Turkenburg, C.S.Verma, M.A.Walsh, and G.Grogan (2003).
The 2-A crystal structure of 6-oxo camphor hydrolase. New structural diversity in the crotonase superfamily.
  J Biol Chem, 278, 1744-1750.
PDB code: 1o8u
12618183 M.Collinsová, C.Castro, T.A.Garrow, A.Yiotakis, V.Dive, and J.Jirácek (2003).
Combining combinatorial chemistry and affinity chromatography: highly selective inhibitors of human betaine: homocysteine S-methyltransferase.
  Chem Biol, 10, 113-122.  
12409309 T.Hisano, T.Tsuge, T.Fukui, T.Iwata, K.Miki, and Y.Doi (2003).
Crystal structure of the (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis.
  J Biol Chem, 278, 617-624.
PDB code: 1iq6
12445775 A.F.Bell, Y.Feng, H.A.Hofstein, S.Parikh, J.Wu, M.J.Rudolph, C.Kisker, A.Whitty, and P.J.Tonge (2002).
Stereoselectivity of enoyl-CoA hydratase results from preferential activation of one of two bound substrate conformers.
  Chem Biol, 9, 1247-1255.
PDB code: 1mj3
11781327 D.Zhang, W.Yu, B.V.Geisbrecht, S.J.Gould, H.Sprecher, and H.Schulz (2002).
Functional characterization of Delta3,Delta2-enoyl-CoA isomerases from rat liver.
  J Biol Chem, 277, 9127-9132.  
11914498 J.P.Taskinen, T.R.Kiema, K.T.Koivuranta, R.K.Wierenga, and J.K.Hiltunen (2002).
Crystallization and characterization of the dehydrogenase domain from rat peroxisomal multifunctional enzyme type 1.
  Acta Crystallogr D Biol Crystallogr, 58, 690-693.  
12192069 S.Chakraborty, N.Chakraborty, D.Jain, D.M.Salunke, and A.Datta (2002).
Active site geometry of oxalate decarboxylase from Flammulina velutipes: Role of histidine-coordinated manganese in substrate recognition.
  Protein Sci, 11, 2138-2147.  
11327833 A.F.Bell, J.Wu, Y.Feng, and P.J.Tonge (2001).
Involvement of glycine 141 in substrate activation by enoyl-CoA hydratase.
  Biochemistry, 40, 1725-1733.  
11395407 J.A.Gerlt, and P.C.Babbitt (2001).
Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies.
  Annu Rev Biochem, 70, 209-246.  
11134939 T.Hisano, T.Fukui, T.Iwata, and Y.Doi (2001).
Crystallization and preliminary X-ray analysis of (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis.
  Acta Crystallogr D Biol Crystallogr, 57, 145-147.  
10944342 A.M.Mursula, D.M.van Aalten, Y.Modis, J.K.Hiltunen, and R.K.Wierenga (2000).
Crystallization and X-ray diffraction analysis of peroxisomal Delta3-Delta2-enoyl-CoA isomerase from Saccharomyces cerevisiae.
  Acta Crystallogr D Biol Crystallogr, 56, 1020-1023.  
11050437 B.Kobe, and A.V.Kajava (2000).
When protein folding is simplified to protein coiling: the continuum of solenoid protein structures.
  Trends Biochem Sci, 25, 509-515.  
  11178260 J.A.Gerlt, and P.C.Babbitt (2000).
Can sequence determine function?
  Genome Biol, 1, REVIEWS0005.  
10836749 J.C.Lim, J.Lee, J.D.Jang, J.Y.Lim, K.R.Min, C.K.Kim, and Y.Kim (2000).
Characterization of the pcbE gene encoding 2-hydroxypenta-2,4-dienoate hydratase in Pseudomonas sp. DJ-12.
  Arch Pharm Res, 23, 187-195.  
11009615 J.F.Baker-Malcolm, M.Lantz, V.E.Anderson, and C.Thorpe (2000).
Novel inactivation of enoyl-CoA hydratase via beta-elimination of 5, 6-dichloro-7,7,7-trifluoro-4-thia-5-heptenoyl-CoA.
  Biochemistry, 39, 12007-12018.  
10841782 K.L.Fillgrove, and V.E.Anderson (2000).
Orientation of coenzyme A substrates, nicotinamide and active site functional groups in (Di)enoyl-coenzyme A reductases.
  Biochemistry, 39, 7001-7011.  
10769118 M.M.Benning, T.Haller, J.A.Gerlt, and H.M.Holden (2000).
New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli.
  Biochemistry, 39, 4630-4639.
PDB codes: 1ef8 1ef9
10849007 S.Dickert, A.J.Pierik, D.Linder, and W.Buckel (2000).
The involvement of coenzyme A esters in the dehydration of (R)-phenyllactate to (E)-cinnamate by Clostridium sporogenes.
  Eur J Biochem, 267, 3874-3884.  
10769117 T.Haller, T.Buckel, J.Rétey, and J.A.Gerlt (2000).
Discovering new enzymes and metabolic pathways: conversion of succinate to propionate by Escherichia coli.
  Biochemistry, 39, 4622-4629.  
10651637 T.M.Stanley, W.H.Johnson, E.A.Burks, C.P.Whitman, C.C.Hwang, and P.F.Cook (2000).
Expression and stereochemical and isotope effect studies of active 4-oxalocrotonate decarboxylase.
  Biochemistry, 39, 718-726.  
10671535 Y.M.Qin, A.M.Haapalainen, S.H.Kilpeläinen, M.S.Marttila, M.K.Koski, T.Glumoff, D.K.Novikov, and J.K.Hiltunen (2000).
Human peroxisomal multifunctional enzyme type 2. Site-directed mutagenesis studies show the importance of two protic residues for 2-enoyl-CoA hydratase 2 activity.
  J Biol Chem, 275, 4965-4972.  
10387003 H.Xiang, L.Luo, K.L.Taylor, and D.Dunaway-Mariano (1999).
Interchange of catalytic activity within the 2-enoyl-coenzyme A hydratase/isomerase superfamily based on a common active site template.
  Biochemistry, 38, 7638-7652.  
10231530 J.J.Barycki, L.K.O'Brien, J.M.Bratt, R.Zhang, R.Sanishvili, A.W.Strauss, and L.J.Banaszak (1999).
Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.
  Biochemistry, 38, 5786-5798.
PDB codes: 2hdh 3had
10205156 T.Izard, and A.Geerlof (1999).
The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity.
  EMBO J, 18, 2021-2030.
PDB code: 1b6t
10074351 T.R.Kiema, C.K.Engel, W.Schmitz, S.A.Filppula, R.K.Wierenga, and J.K.Hiltunen (1999).
Mutagenic and enzymological studies of the hydratase and isomerase activities of 2-enoyl-CoA hydratase-1.
  Biochemistry, 38, 2991-2999.  
10497229 Y.M.Qin, M.S.Marttila, A.M.Haapalainen, K.M.Siivari, T.Glumoff, and J.K.Hiltunen (1999).
Yeast peroxisomal multifunctional enzyme: (3R)-hydroxyacyl-CoA dehydrogenase domains A and B are required for optimal growth on oleic acid.
  J Biol Chem, 274, 28619-28625.  
9666335 A.G.Murzin (1998).
How far divergent evolution goes in proteins.
  Curr Opin Struct Biol, 8, 380-387.  
9813046 A.Gurvitz, A.M.Mursula, A.Firzinger, B.Hamilton, S.H.Kilpeläinen, A.Hartig, H.Ruis, J.K.Hiltunen, and H.Rottensteiner (1998).
Peroxisomal Delta3-cis-Delta2-trans-enoyl-CoA isomerase encoded by ECI1 is required for growth of the yeast Saccharomyces cerevisiae on unsaturated fatty acids.
  J Biol Chem, 273, 31366-31374.  
  9573182 D.A.Pelletier, and C.S.Harwood (1998).
2-Ketocyclohexanecarboxyl coenzyme A hydrolase, the ring cleavage enzyme required for anaerobic benzoate degradation by Rhodopseudomonas palustris.
  J Bacteriol, 180, 2330-2336.  
9818186 J.A.Gerlt, and P.C.Babbitt (1998).
Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis.
  Curr Opin Chem Biol, 2, 607-612.  
9417087 S.A.Filppula, A.I.Yagi, S.H.Kilpeläinen, D.Novikov, D.R.FitzPatrick, M.Vihinen, D.Valle, and J.K.Hiltunen (1998).
Delta3,5-delta2,4-dienoyl-CoA isomerase from rat liver. Molecular characterization.
  J Biol Chem, 273, 349-355.  
9539706 Y.J.Zheng, and T.C.Bruice (1998).
Role of a critical water in scytalone dehydratase-catalyzed reaction.
  Proc Natl Acad Sci U S A, 95, 4158-4163.  
9108262 J.Nakagawa, and C.Moroni (1997).
A 20-amino-acid autonomous RNA-binding domain contained in an enoyl-CoA hydratase.
  Eur J Biochem, 244, 890-899.  
9388188 P.C.Babbitt, and J.A.Gerlt (1997).
Understanding enzyme superfamilies. Chemistry As the fundamental determinant in the evolution of new catalytic activities.
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9115409 S.D.Copley (1997).
Diverse mechanistic approaches to difficult chemical transformations: microbial dehalogenation of chlorinated aromatic compounds.
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9283097 X.Y.He, and S.Y.Yang (1997).
Glutamate-119 of the large alpha-subunit is the catalytic base in the hydration of 2-trans-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli.
  Biochemistry, 36, 11044-11049.  
8994879 C.Engel, and R.Wierenga (1996).
The diverse world of coenzyme A binding proteins.
  Curr Opin Struct Biol, 6, 790-797.  
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.