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PDBsum entry 1v25
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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
1v25

 

 

 

 

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Contents
Protein chains
491 a.a. *
Ligands
ANP ×2
Metals
_MG ×2
Waters ×421
* Residue conservation analysis
PDB id:
1v25
Name: Ligase
Title: Crystal structure of tt0168 from thermus thermophilus hb8
Structure: Long-chain-fatty-acid-coa synthetase. Chain: a, b. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.208     R-free:   0.240
Authors: Y.Hisanaga,H.Ago,T.Nakatsu,K.Hamada,K.Ida,H.Kanda,M.Yamamoto,T.Hori, Y.Arii,M.Sugahara,S.Kuramitsu,S.Yokoyama,M.Miyano,Riken Structural Genomics/proteomics Initiative (Rsgi)
Key ref:
Y.Hisanaga et al. (2004). Structural basis of the substrate-specific two-step catalysis of long chain fatty acyl-CoA synthetase dimer. J Biol Chem, 279, 31717-31726. PubMed id: 15145952 DOI: 10.1074/jbc.M400100200
Date:
07-Oct-03     Release date:   27-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q5SKN9  (LCFCS_THET8) -  Long-chain-fatty-acid--CoA ligase from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		 
Seq:
Struc: 		541 a.a.
491 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.2.1.3  - long-chain-fatty-acid--CoA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate
long-chain fatty acid
 + ATP
 + CoA
 = long-chain fatty acyl-CoA
 +
AMP
Bound ligand (Het Group name = ANP)
matches with 74.19% similarity 		+ diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M400100200 J Biol Chem 279:31717-31726 (2004)
PubMed id: 15145952  
 
 
Structural basis of the substrate-specific two-step catalysis of long chain fatty acyl-CoA synthetase dimer.
Y.Hisanaga, H.Ago, N.Nakagawa, K.Hamada, K.Ida, M.Yamamoto, T.Hori, Y.Arii, M.Sugahara, S.Kuramitsu, S.Yokoyama, M.Miyano.
 
  ABSTRACT  
 
Long chain fatty acyl-CoA synthetases are responsible for fatty acid degradation as well as physiological regulation of cellular functions via the production of long chain fatty acyl-CoA esters. We report the first crystal structures of long chain fatty acyl-CoA synthetase homodimer (LC-FACS) from Thermus thermophilus HB8 (ttLC-FACS), including complexes with the ATP analogue adenosine 5'-(beta,gamma-imido) triphosphate (AMP-PNP) and myristoyl-AMP. ttLC-FACS is a member of the adenylate forming enzyme superfamily that catalyzes the ATP-dependent acylation of fatty acid in a two-step reaction. The first reaction step was shown to propagate in AMP-PNP complex crystals soaked with myristate solution. Myristoyl-AMP was identified as the intermediate. The AMP-PNP and the myristoyl-AMP complex structures show an identical closed conformation of the small C-terminal domains, whereas the uncomplexed form shows a variety of open conformations. Upon ATP binding, the fatty acid-binding tunnel gated by an aromatic residue opens to the ATP-binding site. The gated fatty acid-binding tunnel appears only to allow one-way movement of the fatty acid during overall catalysis. The protein incorporates a hydrophobic branch from the fatty acid-binding tunnel that is responsible for substrate specificity. Based on these high resolution crystal structures, we propose a unidirectional Bi Uni Uni Bi Ping-Pong mechanism for the two-step acylation by ttLC-FACS.
 
  Selected figure(s)  
 
Figure 3.
FIG. 3. ttLC-FACS crystal structure. Ribbon representations of the ttLC-FACS dimer are shown (A). In the panel, the secondary structure of the C-terminal domain is colored in green. In the N-terminal domain, -helix and -sheet are colored in cyan and red, respectively, with the N-terminal domain-swapping peptide colored in yellow. The electrostatic potential surface map of ttLC-FACS dimer in the same orientation as the representation in A. Red represents negatively charged regions, and blue represents positively charged regions (B). Close-up view of the N-terminal peptide involved in domain swapping in the reverse orientation view to A (C). Residues with carbons colored in pink against a cyan surface of one monomer interacts with the concave surface of the other monomer colored in yellow. There are salt bridges at the domain swapping region. The monomer of ttLC-FACS with each secondary structure feature is labeled according to the scheme given in Fig. 2A (D). 		Figure 6.
FIG. 6. Superimposed structures of the vicinity of linker peptides and bound adenylates in adenylate forming enzyme complexes in stereo. The adenylate complexed enzymes of the known structures, DhbE (Protein Data Bank code 1mdb [PDB] ) (30), PheA (Protein Data Bank code 1amu [PDB] ) (29), SC-FACS (Protein Data Bank code 1pg3 [PDB] ) (31), and ttLC-FACS (this work) are superimposed around each bound adenosine moiety. The backbone of the linker region (Lys431-Asp-Arg-Leu-Lys-Asp-Leu437) including the L motif in ttLC-FACS complex structure and the corresponding peptides are presented as wire models (ttLC-FACS, thick violet; SC-FACS, red violet; DhbE, blue; PheA, light green). The bound myristoyl-AMP in the ttLC-FACS is represented as by thick green sticks, and other bound adenylates each shown in thin colored sticks. Arg433 and Lys439 of ttLC-FACS and the corresponding residues are also shown.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 31717-31726) copyright 2004.  
  Figures were selected by the author.  

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
20454815 N.Jatana, S.Jangid, G.Khare, A.K.Tyagi, and N.Latha (2011).
Molecular modeling studies of Fatty acyl-CoA synthetase (FadD13) from Mycobacterium tuberculosis-a potential target for the development of antitubercular drugs.
  J Mol Model, 17, 301-313.  
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
21150124 D.Kato, H.Yoshida, M.Takeo, S.Negoro, and H.Ohta (2010).
Purification and gene cloning of an enantioselective thioesterification enzyme from Brevibacterium ketoglutamicum KU1073, a deracemization bacterium of 2-(4-chlorophenoxy)propanoic acid.
  Biosci Biotechnol Biochem, 74, 2405-2412.  
20429931 E.Soupene, N.P.Dinh, M.Siliakus, and F.A.Kuypers (2010).
Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains.
  BMC Biochem, 11, 18.  
20979641 J.Hedlund, H.Jörnvall, and B.Persson (2010).
Subdivision of the MDR superfamily of medium-chain dehydrogenases/reductases through iterative hidden Markov model refinement.
  BMC Bioinformatics, 11, 534.  
20642725 J.K.Weng, and C.Chapple (2010).
The origin and evolution of lignin biosynthesis.
  New Phytol, 187, 273-285.  
19818872 L.O.Li, E.L.Klett, and R.A.Coleman (2010).
Acyl-CoA synthesis, lipid metabolism and lipotoxicity.
  Biochim Biophys Acta, 1801, 246-251.  
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
  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
19182784 P.Arora, A.Goyal, V.T.Natarajan, E.Rajakumara, P.Verma, R.Gupta, M.Yousuf, O.A.Trivedi, D.Mohanty, A.Tyagi, R.Sankaranarayanan, and R.S.Gokhale (2009).
Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.
  Nat Chem Biol, 5, 166-173.
PDB code: 3e53
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
18620418 A.S.Reger, R.Wu, D.Dunaway-Mariano, and A.M.Gulick (2008).
Structural characterization of a 140 degrees domain movement in the two-step reaction catalyzed by 4-chlorobenzoate:CoA ligase.
  Biochemistry, 47, 8016-8025.
PDB codes: 3cw8 3cw9
17985114 A.Tani, P.Somyoonsap, T.Minami, K.Kimbara, and F.Kawai (2008).
Polyethylene glycol (PEG)-carboxylate-CoA synthetase is involved in PEG metabolism in Sphingopyxis macrogoltabida strain 103.
  Arch Microbiol, 189, 407-410.  
18568158 J.S.Cisar, and D.S.Tan (2008).
Small molecule inhibition of microbial natural product biosynthesis-an emerging antibiotic strategy.
  Chem Soc Rev, 37, 1320-1329.  
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.  
18762421 X.Lu, H.Zhang, P.J.Tonge, and D.S.Tan (2008).
Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis.
  Bioorg Med Chem Lett, 18, 5963-5966.  
17996401 Y.Oba, K.Iida, M.Ojika, and S.Inouye (2008).
Orthologous gene of beetle luciferase in non-luminous click beetle, Agrypnus binodulus (Elateridae), encodes a fatty acyl-CoA synthetase.
  Gene, 407, 169-175.  
17497934 A.S.Reger, J.M.Carney, and A.M.Gulick (2007).
Biochemical and crystallographic analysis of substrate binding and conformational changes in acetyl-CoA synthetase.
  Biochemistry, 46, 6536-6546.
PDB codes: 2p20 2p2b 2p2f 2p2j 2p2m 2p2q
  18024611 F.A.Kuypers (2007).
Membrane lipid alterations in hemoglobinopathies.
  Hematology Am Soc Hematol Educ Program, 2007, 68-73.  
17604220 H.Li, E.M.Melton, S.Quackenbush, C.C.DiRusso, and P.N.Black (2007).
Mechanistic studies of the long chain acyl-CoA synthetase Faa1p from Saccharomyces cerevisiae.
  Biochim Biophys Acta, 1771, 1246-1253.  
17110164 L.Stinnett, T.M.Lewin, and R.A.Coleman (2007).
Mutagenesis of rat acyl-CoA synthetase 4 indicates amino acids that contribute to fatty acid binding.
  Biochim Biophys Acta, 1771, 119-125.  
17522836 R.Bränström, I.B.Leibiger, B.Leibiger, G.Klement, J.Nilsson, P.Arhem, C.A.Aspinwall, B.E.Corkey, O.Larsson, and P.O.Berggren (2007).
Single residue (K332A) substitution in Kir6.2 abolishes the stimulatory effect of long-chain acyl-CoA esters: indications for a long-chain acyl-CoA ester binding motif.
  Diabetologia, 50, 1670-1677.  
16790016 E.Arias-Barrau, E.R.Olivera, A.Sandoval, G.Naharro, and J.M.Luengo (2006).
Acetyl-CoA synthetase from Pseudomonas putida U is the only acyl-CoA activating enzyme induced by acetate in this bacterium.
  FEMS Microbiol Lett, 260, 36-46.  
16632253 E.J.Drake, D.A.Nicolai, and A.M.Gulick (2006).
Structure of the EntB multidomain nonribosomal peptide synthetase and functional analysis of its interaction with the EntE adenylation domain.
  Chem Biol, 13, 409-419.
PDB code: 2fq1
16834775 E.Soupene, and F.A.Kuypers (2006).
Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains.
  BMC Mol Biol, 7, 21.  
17090919 Y.Oba, K.Tanaka, and S.Inouye (2006).
Catalytic properties of domain-exchanged chimeric proteins between firefly luciferase and Drosophila fatty Acyl-CoA synthetase CG6178.
  Biosci Biotechnol Biochem, 70, 2739-2744.  
16756548 Y.Oba, M.Sato, and S.Inouye (2006).
Cloning and characterization of the homologous genes of firefly luciferase in the mealworm beetle, Tenebrio molitor.
  Insect Mol Biol, 15, 293-299.  
16459927 D.Maoz, H.J.Lee, J.Deutsch, S.I.Rapoport, and R.P.Bazinet (2005).
Immediate no-flow ischemia decreases rat heart nonesterified fatty acid and increases acyl-CoA species concentrations.
  Lipids, 40, 1149-1154.  
16115688 K.C.Onwueme, C.J.Vos, J.Zurita, J.A.Ferreras, and L.E.Quadri (2005).
The dimycocerosate ester polyketide virulence factors of mycobacteria.
  Prog Lipid Res, 44, 259-302.  
15767857 R.M.Fisher, and K.Gertow (2005).
Fatty acid transport proteins and insulin resistance.
  Curr Opin Lipidol, 16, 173-178.  
15849423 Y.Oba, M.Sato, M.Ojika, and S.Inouye (2005).
Enzymatic and genetic characterization of firefly luciferase and Drosophila CG6178 as a fatty acyl-CoA synthetase.
  Biosci Biotechnol Biochem, 69, 819-828.  
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.

 

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