PDBsum entry 3cw9

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
503 a.a. *
AMP ×2
01A ×2
NO3 ×3
_MG ×2
Waters ×800
* Residue conservation analysis
PDB id:
Name: Ligase
Title: 4-chlorobenzoyl-coa ligase/synthetase in the thioester-formi conformation, bound to 4-chlorophenacyl-coa
Structure: 4-chlorobenzoyl coa ligase. Chain: a, b. Synonym: chlorobenzoate coa ligase/synthetase. Engineered: yes
Source: Alcaligenes sp.. Strain: al3007. Expressed in: escherichia coli.
2.00Å     R-factor:   0.168     R-free:   0.209
Authors: A.S.Reger,J.Cao,R.Wu,D.Dunaway-Mariano,A.M.Gulick
Key ref: A.S.Reger et al. (2008). Structural characterization of a 140 degrees domain movement in the two-step reaction catalyzed by 4-chlorobenzoate:CoA ligase. Biochemistry, 47, 8016-8025. PubMed id: 18620418
21-Apr-08     Release date:   02-Sep-08    
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Protein chains
Pfam   ArchSchema ?
Q8GN86  (Q8GN86_9BURK) -  4-chlorobenzoyl CoA ligase
504 a.a.
503 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     4 terms  


Biochemistry 47:8016-8025 (2008)
PubMed id: 18620418  
Structural characterization of a 140 degrees domain movement in the two-step reaction catalyzed by 4-chlorobenzoate:CoA ligase.
A.S.Reger, R.Wu, D.Dunaway-Mariano, A.M.Gulick.
Members of the adenylate-forming family of enzymes play a role in the metabolism of halogenated aromatics and of short, medium, and long chain fatty acids, as well as in the biosynthesis of menaquinone, peptide antibiotics, and peptide siderophores. This family includes a subfamily of acyl- and aryl-CoA ligases that catalyze thioester synthesis through two half-reactions. A carboxylate substrate first reacts with ATP to form an acyl-adenylate. Subsequent to the release of the product PP i, the enzyme binds CoA, which attacks the activated acyl group to displace AMP. Structural and functional studies on different family members suggest that these enzymes alternate between two conformations during catalysis of the two half-reactions. Specifically, after the initial adenylation step, the C-terminal domain rotates by approximately 140 degrees to adopt a second conformation for thioester formation. Previously, we determined the structure of 4-chlorobenzoate:CoA ligase (CBL) in the adenylate forming conformation bound to 4-chlorobenzoate. We have determined two new crystal structures. We have determined the structure of CBL in the original adenylate-forming conformation, bound to the adenylate intermediate. Additionally, we have used a novel product analogue, 4-chlorophenacyl-CoA, to trap the enzyme in the thioester-forming conformation and determined this structure in a new crystal form. This work identifies a novel binding pocket for the CoA nucleotide. The structures presented herein provide the foundation for biochemical analyses presented in the accompanying manuscript in this issue [Wu et al. (2008) Biochemistry 47, 8026-8039]. The complete characterization of this enzyme allows us to provide an explanation for the use of the domain alternation strategy by these enzymes.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21338915 A.J.Hughes, and A.Keatinge-Clay (2011).
Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and functional showcasing of Streptomyces coelicolor MatB.
  Chem Biol, 18, 165-176.
PDB codes: 3nyq 3nyr
20516619 A.K.Bera, V.Atanasova, S.Gamage, H.Robinson, and J.F.Parsons (2010).
Structure of the D-alanylgriseoluteic acid biosynthetic protein EhpF, an atypical member of the ANL superfamily of adenylating enzymes.
  Acta Crystallogr D Biol Crystallogr, 66, 664-672.
PDB code: 3l2k
20089862 K.Fujiwara, N.Maita, H.Hosaka, K.Okamura-Ikeda, A.Nakagawa, and H.Taniguchi (2010).
Global conformational change associated with the two-step reaction catalyzed by Escherichia coli lipoate-protein ligase A.
  J Biol Chem, 285, 9971-9980.
PDB codes: 3a7a 3a7l 3a7r 3a7u
19923209 T.V.Lee, L.J.Johnson, R.D.Johnson, A.Koulman, G.A.Lane, J.S.Lott, and V.L.Arcus (2010).
Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis.
  J Biol Chem, 285, 2415-2427.
PDB code: 3ite
19219015 A.M.Gulick (2009).
Ironing out a new siderophore synthesis strategy.
  Nat Chem Biol, 5, 143-144.
PDB code: 3ffe
  19610673 A.M.Gulick (2009).
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
  ACS Chem Biol, 4, 811-827.  
19544569 M.B.Shah, C.Ingram-Smith, L.L.Cooper, J.Qu, Y.Meng, K.S.Smith, and A.M.Gulick (2009).
The 2.1 A crystal structure of an acyl-CoA synthetase from Methanosarcina acetivorans reveals an alternate acyl-binding pocket for small branched acyl substrates.
  Proteins, 77, 685-698.
PDB code: 3etc
19320426 R.Wu, A.S.Reger, X.Lu, A.M.Gulick, and D.Dunaway-Mariano (2009).
The mechanism of domain alternation in the acyl-adenylate forming ligase superfamily member 4-chlorobenzoate: coenzyme A ligase.
  Biochemistry, 48, 4115-4125.
PDB code: 3dlp
18959760 M.Wittmann, U.Linne, V.Pohlmann, and M.A.Marahiel (2008).
Role of DptE and DptF in the lipidation reaction of daptomycin.
  FEBS J, 275, 5343-5354.  
18973344 Y.Tian, D.H.Suk, F.Cai, D.Crich, and A.D.Mesecar (2008).
Bacillus anthracis o-succinylbenzoyl-CoA synthetase: reaction kinetics and a novel inhibitor mimicking its reaction intermediate.
  Biochemistry, 47, 12434-12447.  
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