PDBsum entry 1nzy

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
269 a.a. *
BCA ×3
EDO ×2
_CA ×3
Waters ×598
* Residue conservation analysis
PDB id:
Name: Lyase
Title: 4-chlorobenzoyl coenzyme a dehalogenase from pseudomonas sp. Cbs-3
Structure: 4-chlorobenzoyl coenzyme a dehalogenase. Chain: a, c. Synonym: dehalogenase. Engineered: yes. 4-chlorobenzoyl coenzyme a dehalogenase. Chain: b. Synonym: dehalogenase. Engineered: yes
Source: Pseudomonas sp.. Organism_taxid: 72586. Strain: cbs-3. Expressed in: escherichia coli. Expression_system_taxid: 562. Pseudomonas sp. Cbs3. Expression_system_taxid: 562
Biol. unit: Hexamer (from PQS)
1.80Å     R-factor:   0.188    
Authors: M.M.Benning,H.M.Holden
Key ref:
M.M.Benning et al. (1996). Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation. Biochemistry, 35, 8103-8109. PubMed id: 8679561 DOI: 10.1021/bi960768p
02-Apr-96     Release date:   07-Jul-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
A5JTM5  (CBADH_PSEUC) -  4-chlorobenzoyl coenzyme A dehalogenase
269 a.a.
269 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - 4-chlorobenzoyl-CoA dehalogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-chlorobenzoyl-CoA + H2O = 4-hydroxybenzoyl CoA + chloride
+ H(2)O
4-hydroxybenzoyl CoA
Bound ligand (Het Group name = BCA)
matches with 92.98% similarity
+ chloride
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     3 terms  


    Added reference    
DOI no: 10.1021/bi960768p Biochemistry 35:8103-8109 (1996)
PubMed id: 8679561  
Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation.
M.M.Benning, K.L.Taylor, Liu R-Q, G.Yang, H.Xiang, G.Wesenberg, D.Dunaway-Mariano, H.M.Holden.
Here we describe the three-dimensional structure of 4-chlorobenzoyl-CoA dehalogenase from Pseudomonas sp. strain CBS-3. This enzyme catalyzes the hydrolysis of 4-chlorobenzoyl-CoA to 4-hydroxybenzoyl-CoA. The molecular structure of the enzyme/4-hydroxybenzoyl-CoA complex was solved by the techniques of multiple isomorphous replacement, solvent flattening, and molecular averaging. Least-squares refinement of the protein model reduced the crystallographic R factor to 18.8% for all measured X-ray data from 30 to 1.8 A resolution. The crystallographic investigation of this dehalogenase revealed that the enzyme is a trimer. Each subunit of the trimer folds into two distinct motifs. The larger, N-terminal domain is characterized by 10 strands of beta-pleated sheet that form two distinct layers which lie nearly perpendicular to one another. These layers of beta-sheet are flanked on either side by alpha-helices. The C-terminal domain extends away from the body of the molecule and is composed of three amphiphilic alpha-helices. This smaller domain is primarily involved in trimerization. The two domains of the subunit are linked together by a cation, most likely a calcium ion. The 4-hydroxybenzoyl-CoA molecule adopts a curved conformation within the active site such that the 4-hydroxybenzoyl and the adenosine moieties are buried while the pantothenate and pyrophosphate groups of the coenzyme are more solvent exposed. From the three-dimensional structure it is clear that Asp 145 provides the side-chain carboxylate group that adds to form the Meisenheimer intermediate and His 90 serves as the general base in the subsequent hydrolysis step. Many of the structural principles derived from this investigation may be directly applicable to other related enzymes such as crotonase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19856961 B.A.Robertson, G.K.Schroeder, Z.Jin, K.A.Johnson, and C.P.Whitman (2009).
Pre-steady-state kinetic analysis of cis-3-chloroacrylic acid dehalogenase: analysis and implications.
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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.
  J Biol Chem, 284, 16377-16385.
PDB code: 2w3p
19221587 K.Chen, and L.Kurgan (2009).
Investigation of atomic level patterns in protein--small ligand interactions.
  PLoS ONE, 4, e4473.  
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.
  Proteins, 75, 360-372.
PDB codes: 2zqq 2zqr
17431803 L.Zhou, R.P.Poh, T.S.Marks, B.Z.Chowdhry, and A.R.Smith (2008).
Structure and denaturation of 4-chlorobenzoyl coenzyme A dehalogenase from Arthrobacter sp. strain TM-1.
  Biodegradation, 19, 65-75.  
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Expression, purification and preliminary X-ray characterization of DL-2-haloacid dehalogenase from Methylobacterium sp. CPA1.
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17530074 S.M.Butterfield, and J.Rebek (2007).
A cavitand stabilizes the Meisenheimer complex of SNAr reactions.
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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
  17200656 J.M.Nickerson, R.A.Frey, V.T.Ciavatta, and D.L.Stenkamp (2006).
Interphotoreceptor retinoid-binding protein gene structure in tetrapods and teleost fish.
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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.
  Acta Crystallogr D Biol Crystallogr, 62, 1494-1501.
PDB code: 2j5i
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
15625671 Z.Zhong, B.J.Postnikova, R.E.Hanes, V.M.Lynch, and E.V.Anslyn (2005).
Large pKa shifts of alpha-carbon acids induced by copper(II) complexes.
  Chemistry, 11, 2385-2394.  
14625287 M.C.Sleeman, and C.J.Schofield (2004).
Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carbapenem biosynthesis.
  J Biol Chem, 279, 6730-6736.  
15583385 P.M.Leonard, C.M.Marshall, E.J.Dodson, N.J.Walton, and G.Grogan (2004).
Purification, crystallization and preliminary X-ray crystallographic analysis of hydroxycinnamoyl-coenzyme A hydratase-lyase (HCHL), a crotonase homologue active in phenylpropanoid metabolism.
  Acta Crystallogr D Biol Crystallogr, 60, 2343-2345.  
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
14701869 Jong, W.Brugman, G.J.Poelarends, C.P.Whitman, and B.W.Dijkstra (2004).
The X-ray structure of trans-3-chloroacrylic acid dehalogenase reveals a novel hydration mechanism in the tautomerase superfamily.
  J Biol Chem, 279, 11546-11552.
PDB code: 1s0y
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
12853465 K.S.Wendt, I.Schall, R.Huber, W.Buckel, and U.Jacob (2003).
Crystal structure of the carboxyltransferase subunit of the bacterial sodium ion pump glutaconyl-coenzyme A decarboxylase.
  EMBO J, 22, 3493-3502.
PDB code: 1pix
12743028 P.R.Hall, Y.F.Wang, R.E.Rivera-Hainaj, X.Zheng, M.Pustai-Carey, P.R.Carey, and V.C.Yee (2003).
Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core.
  EMBO J, 22, 2334-2347.
PDB codes: 1on3 1on9
14675551 Jong, and B.W.Dijkstra (2003).
Structure and mechanism of bacterial dehalogenases: different ways to cleave a carbon-halogen bond.
  Curr Opin Struct Biol, 13, 722-730.  
12732540 Z.Zhuang, K.H.Gartemann, R.Eichenlaub, and D.Dunaway-Mariano (2003).
Characterization of the 4-hydroxybenzoyl-coenzyme A thioesterase from Arthrobacter sp. strain SU.
  Appl Environ Microbiol, 69, 2707-2711.  
11796109 A.Loew, and F.Gonzalez-Fernandez (2002).
Crystal structure of the functional unit of interphotoreceptor retinoid binding protein.
  Structure, 10, 43-49.
PDB code: 1j7x
12044179 J.Dong, P.R.Carey, Y.Wei, L.Luo, X.Lu, R.Q.Liu, and D.Dunaway-Mariano (2002).
Raman evidence for Meisenheimer complex formation in the hydrolysis reactions of 4-fluorobenzoyl- and 4-nitrobenzoyl-coenzyme A catalyzed by 4-chlorobenzoyl-coenzyme A dehalogenase.
  Biochemistry, 41, 7453-7463.  
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.  
11493680 E.Y.Lau, and T.C.Bruice (2001).
The active site dynamics of 4-chlorobenzoyl-CoA dehalogenase.
  Proc Natl Acad Sci U S A, 98, 9527-9532.  
11418568 G.J.Poelarends, R.Saunier, and D.B.Janssen (2001).
trans-3-Chloroacrylic acid dehalogenase from Pseudomonas pavonaceae 170 shares structural and mechanistic similarities with 4-oxalocrotonate tautomerase.
  J Bacteriol, 183, 4269-4277.  
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.  
11274097 J.L.Seffernick, Souza, M.J.Sadowsky, and L.P.Wackett (2001).
Melamine deaminase and atrazine chlorohydrolase: 98 percent identical but functionally different.
  J Bacteriol, 183, 2405-2410.  
11738050 K.Kurimoto, S.Fukai, O.Nureki, Y.Muto, and S.Yokoyama (2001).
Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase.
  Structure, 9, 1253-1263.
PDB code: 1hzd
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.  
  11178260 J.A.Gerlt, and P.C.Babbitt (2000).
Can sequence determine function?
  Genome Biol, 1, REVIEWS0005.  
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
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.  
10350485 D.Dinakarpandian, B.C.Shenoy, D.Hilvert, D.E.McRee, M.McTigue, and P.R.Carey (1999).
Electric fields in active sites: substrate switching from null to strong fields in thiol- and selenol-subtilisins.
  Biochemistry, 38, 6659-6667.
PDB code: 1ubn
10194337 H.Xiang, J.Dong, P.R.Carey, and D.Dunaway-Mariano (1999).
Product catalyzes the deamidation of D145N dehalogenase to produce the wild-type enzyme.
  Biochemistry, 38, 4207-4213.  
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.  
10521454 I.S.Ridder, H.J.Rozeboom, K.H.Kalk, and B.W.Dijkstra (1999).
Crystal structures of intermediates in the dehalogenation of haloalkanoates by L-2-haloacid dehalogenase.
  J Biol Chem, 274, 30672-30678.
PDB codes: 1qq5 1qq6 1qq7
10194336 J.Dong, H.Xiang, L.Luo, D.Dunaway-Mariano, and P.R.Carey (1999).
Modulating electron density in the bound product, 4-hydroxybenzoyl-CoA, by mutations in 4-chlorobenzoyl-CoA dehalogenase near the 4-hydroxy group.
  Biochemistry, 38, 4198-4206.  
10480862 P.R.Carey (1999).
Raman spectroscopy, the sleeping giant in structural biology, awakes.
  J Biol Chem, 274, 26625-26628.  
10409645 V.Nardi-Dei, T.Kurihara, C.Park, M.Miyagi, S.Tsunasawa, K.Soda, and N.Esaki (1999).
DL-2-Haloacid dehalogenase from Pseudomonas sp. 113 is a new class of dehalogenase catalyzing hydrolytic dehalogenation not involving enzyme-substrate ester intermediate.
  J Biol Chem, 274, 20977-20981.  
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.  
9837940 M.M.Benning, G.Wesenberg, R.Liu, K.L.Taylor, D.Dunaway-Mariano, and H.M.Holden (1998).
The three-dimensional structure of 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Strain CBS-3.
  J Biol Chem, 273, 33572-33579.
PDB code: 1bvq
9667912 R.J.Kazlauskas, and H.K.Weber (1998).
Improving hydrolases for organic synthesis.
  Curr Opin Chem Biol, 2, 121-126.  
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.  
9818187 S.D.Copley (1998).
Microbial dehalogenases: enzymes recruited to convert xenobiotic substrates.
  Curr Opin Chem Biol, 2, 613-617.  
9614112 Y.F.Li, Y.Hata, T.Fujii, T.Hisano, M.Nishihara, T.Kurihara, and N.Esaki (1998).
Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism.
  J Biol Chem, 273, 15035-15044.
PDB codes: 1zrm 1zrn
9817851 Y.Modis, and R.Wierenga (1998).
Two crystal structures of N-acetyltransferases reveal a new fold for CoA-dependent enzymes.
  Structure, 6, 1345-1350.  
9739087 Y.Modis, S.A.Filppula, D.K.Novikov, B.Norledge, J.K.Hiltunen, and R.K.Wierenga (1998).
The crystal structure of dienoyl-CoA isomerase at 1.5 A resolution reveals the importance of aspartate and glutamate sidechains for catalysis.
  Structure, 6, 957-970.
PDB code: 1dci
9237991 F.C.Lightstone, Y.J.Zheng, A.H.Maulitz, and T.C.Bruice (1997).
Non-enzymatic and enzymatic hydrolysis of alkyl halides: a haloalkane dehalogenation enzyme evolved to stabilize the gas-phase transition state of an SN2 displacement reaction.
  Proc Natl Acad Sci U S A, 94, 8417-8420.  
9407083 I.S.Ridder, H.J.Rozeboom, K.H.Kalk, D.B.Janssen, and B.W.Dijkstra (1997).
Three-dimensional structure of L-2-haloacid dehalogenase from Xanthobacter autotrophicus GJ10 complexed with the substrate-analogue formate.
  J Biol Chem, 272, 33015-33022.
PDB code: 1aq6
9254617 J.Clarkson, P.J.Tonge, K.L.Taylor, D.Dunaway-Mariano, and P.R.Carey (1997).
Raman study of the polarizing forces promoting catalysis in 4-chlorobenzoate-CoA dehalogenase.
  Biochemistry, 36, 10192-10199.  
9063883 K.L.Taylor, H.Xiang, R.Q.Liu, G.Yang, and D.Dunaway-Mariano (1997).
Investigation of substrate activation by 4-chlorobenzoyl-coenzyme A dehalogenase.
  Biochemistry, 36, 1349-1361.  
9388188 P.C.Babbitt, and J.A.Gerlt (1997).
Understanding enzyme superfamilies. Chemistry As the fundamental determinant in the evolution of new catalytic activities.
  J Biol Chem, 272, 30591-30594.  
9115409 S.D.Copley (1997).
Diverse mechanistic approaches to difficult chemical transformations: microbial dehalogenation of chlorinated aromatic compounds.
  Chem Biol, 4, 169-174.  
9047322 W.J.Wu, V.E.Anderson, D.P.Raleigh, and P.J.Tonge (1997).
Structure of hexadienoyl-CoA bound to enoyl-CoA hydratase determined by transferred nuclear Overhauser effect measurements: mechanistic predictions based on the X-ray structure of 4-(chlorobenzoyl)-CoA dehalogenase.
  Biochemistry, 36, 2211-2220.  
8994879 C.Engel, and R.Wierenga (1996).
The diverse world of coenzyme A binding proteins.
  Curr Opin Struct Biol, 6, 790-797.  
8718880 G.Yang, R.Q.Liu, K.L.Taylor, H.Xiang, J.Price, and D.Dunaway-Mariano (1996).
Identification of active site residues essential to 4-chlorobenzoyl-coenzyme A dehalogenase catalysis by chemical modification and site directed mutagenesis.
  Biochemistry, 35, 10879-10885.  
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.