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PDBsum entry 1od2
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protein ligands Protein-protein interface(s) links
Ligase PDB id
1od2

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
720 a.a. *
Ligands
ACO
ADE
Waters ×89
* Residue conservation analysis
PDB id:
1od2
Name: Ligase
Title: Acetyl-coa carboxylase carboxyltransferase domain
Structure: Acetyl-coenzyme a carboxylase. Chain: a, b. Fragment: carboxyltransferase domain, residues 1429-2233. Synonym: acc. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.70Å     R-factor:   0.226     R-free:   0.279
Authors: H.Zhang,Z.Yang,Y.Shen,L.Tong
Key ref:
H.Zhang et al. (2003). Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase. Science, 299, 2064-2067. PubMed id: 12663926 DOI: 10.1126/science.1081366
Date:
12-Feb-03     Release date:   03-Apr-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q00955  (ACAC_YEAST) -  Acetyl-CoA carboxylase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		2233 a.a.
720 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.6.3.4.14  - biotin carboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N6-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = N6- carboxybiotinyl-L-lysyl-[protein] + ADP + phosphate + H+
N(6)-biotinyl-L-lysyl-[protein]
 + hydrogencarbonate
 + ATP
 = N(6)- carboxybiotinyl-L-lysyl-[protein]
Bound ligand (Het Group name = ACO)
matches with 56.25% similarity 		+ ADP
 + phosphate
 + H(+)
   Enzyme class 3: E.C.6.4.1.2  - acetyl-CoA carboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H+
hydrogencarbonate
Bound ligand (Het Group name = ACO)
matches with 94.12% similarity 		+ acetyl-CoA
 + ATP
 = malonyl-CoA
 + ADP
 + phosphate
 + H(+)
      Cofactor: Biotin
Biotin
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

 

 
    reference    
 
 
DOI no: 10.1126/science.1081366 Science 299:2064-2067 (2003)
PubMed id: 12663926  
 
 
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase.
H.Zhang, Z.Yang, Y.Shen, L.Tong.
 
  ABSTRACT  
 
Acetyl-coenzyme A carboxylases (ACCs) are required for the biosynthesis and oxidation of long-chain fatty acids. They are targets for therapeutics against obesity and diabetes, and several herbicides function by inhibiting their carboxyltransferase (CT) domain. We determined the crystal structure of the free enzyme and the coenzyme A complex of yeast CT at 2.7 angstrom resolution and found that it comprises two domains, both belonging to the crotonase/ClpP superfamily. The active site is at the interface of a dimer. Mutagenesis and kinetic studies reveal the functional roles of conserved residues here. The herbicides target the active site of CT, providing a lead for inhibitor development against human ACCs.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Structures of ACCs. (A) Schematic drawing of the primary structures of eukaryotic multidomain ACC and bacterial multisubunit ACC. (B) The chemical reaction catalyzed by CT. The N1 atom of biotin is labeled. (C) Schematic drawing of the structure of the CT domain dimer of yeast ACC. The N and C domains of one monomer are colored cyan and yellow, whereas those of the other monomer are colored purple and green. The CoA molecule bound to one monomer is shown as a stick model. Only the adenine base was observed in the other monomer (labeled A). (C) was produced with Ribbons (22). 		Figure 3.
Fig. 3. The active site of CT and the binding mode of CoA. (A) Schematic drawing in stereo of the active site of CT. The N domain is shown in cyan, and the C domain of the other monomer is shown in green. The side chains of residues in the active site are shown in purple. The prime (') in the labels indicates the C domain of the other monomer of the dimer. (B) Molecular surface of the active site region of CT. The side chain of Lys1764 (in helix 6, 15 Å from the active site) has been removed to facilitate the viewing of the active site. (C) Chemical structure of haloxyfop and the double reciprocal plot showing the competitive inhibition of wild-type yeast CT by haloxyfop. (A) was produced with Ribbons (22), and (B) with Grasp (23).
 
  The above figures are reprinted by permission from the AAAs: Science (2003, 299, 2064-2067) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21455530 E.F.Franca, F.L.Leite, R.A.Cunha, O.N.Oliveira, and L.C.Freitas (2011).
Designing an enzyme-based nanobiosensor using molecular modeling techniques.
  Phys Chem Chem Phys, 13, 8894-8899.  
21204864 G.Gago, L.Diacovich, A.Arabolaza, S.C.Tsai, and H.Gramajo (2011).
Fatty acid biosynthesis in actinomycetes.
  FEMS Microbiol Rev, 35, 475-497.  
20952656 C.L.Colbert, C.W.Kim, Y.A.Moon, L.Henry, M.Palnitkar, W.B.McKean, K.Fitzgerald, J.Deisenhofer, J.D.Horton, and H.J.Kwon (2010).
Crystal structure of Spot 14, a modulator of fatty acid synthesis.
  Proc Natl Acad Sci U S A, 107, 18820-18825.
PDB code: 3ont
20725044 C.S.Huang, K.Sadre-Bazzaz, Y.Shen, B.Deng, Z.H.Zhou, and L.Tong (2010).
Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.
  Nature, 466, 1001-1005.
PDB code: 3n6r
21135213 L.P.Yu, Y.S.Kim, and L.Tong (2010).
Mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by pinoxaden.
  Proc Natl Acad Sci U S A, 107, 22072-22077.
PDB code: 3pgq
20192743 S.B.Powles, and Q.Yu (2010).
Evolution in action: plants resistant to herbicides.
  Annu Rev Plant Biol, 61, 317-347.  
19213731 C.Y.Chou, L.P.Yu, and L.Tong (2009).
Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism.
  J Biol Chem, 284, 11690-11697.
PDB codes: 3g8c 3g8d
19654317 D.Kress, D.Brügel, I.Schall, D.Linder, W.Buckel, and L.O.Essen (2009).
An asymmetric model for Na+-translocating glutaconyl-CoA decarboxylases.
  J Biol Chem, 284, 28401-28409.
PDB codes: 3gf3 3gf7 3glm 3gma
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
19190759 J.C.Castle, Y.Hara, C.K.Raymond, P.Garrett-Engele, K.Ohwaki, Z.Kan, J.Kusunoki, and J.M.Johnson (2009).
ACC2 is expressed at high levels human white adipose and has an isoform with a novel N-terminus.
  PLoS ONE, 4, e4369.  
19390150 K.P.Madauss, W.A.Burkhart, T.G.Consler, D.J.Cowan, W.K.Gottschalk, A.B.Miller, S.A.Short, T.B.Tran, and S.P.Williams (2009).
The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
  Acta Crystallogr D Biol Crystallogr, 65, 449-461.
PDB code: 3ff6
19926852 S.Xiang, M.M.Callaghan, K.G.Watson, and L.Tong (2009).
A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim.
  Proc Natl Acad Sci U S A, 106, 20723-20727.
PDB code: 3k8x
18156466 B.K.Benson, G.Meades, A.Grove, and G.L.Waldrop (2008).
DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: implications for active site communication.
  Protein Sci, 17, 34-42.  
18768797 X.Liu, P.D.Fortin, and C.T.Walsh (2008).
Andrimid producers encode an acetyl-CoA carboxyltransferase subunit resistant to the action of the antibiotic.
  Proc Natl Acad Sci U S A, 105, 13321-13326.  
17298082 A.A.Hoskins, M.Morar, T.J.Kappock, I.I.Mathews, J.B.Zaugg, T.E.Barder, P.Peng, A.Okamoto, S.E.Ealick, and J.Stubbe (2007).
N5-CAIR mutase: role of a CO2 binding site and substrate movement in catalysis.
  Biochemistry, 46, 2842-2855.
PDB codes: 2ate 2nsh 2nsj 2nsl
  17277455 M.Yamada, R.Natsume, T.Nakamatsu, S.Horinouchi, H.Kawasaki, and T.Senda (2007).
Crystallization and preliminary crystallographic analysis of DtsR1, a carboxyltransferase subunit of acetyl-CoA carboxylase from Corynebacterium glutamicum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 120-122.  
16983687 L.Tong, and H.J.Harwood (2006).
Acetyl-coenzyme A carboxylases: versatile targets for drug discovery.
  J Cell Biochem, 99, 1476-1488.  
16492739 T.W.Lin, M.M.Melgar, D.Kurth, S.J.Swamidass, J.Purdon, T.Tseng, G.Gago, P.Baldi, H.Gramajo, and S.C.Tsai (2006).
Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis.
  Proc Natl Acad Sci U S A, 103, 3072-3077.
PDB code: 2a7s
16793549 Y.Shen, C.Y.Chou, G.G.Chang, and L.Tong (2006).
Is dimerization required for the catalytic activity of bacterial biotin carboxylase?
  Mol Cell, 22, 807-818.
PDB codes: 2gps 2gpw
15341732 H.Zhang, B.Tweel, J.Li, and L.Tong (2004).
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186.
  Structure, 12, 1683-1691.
PDB code: 1w2x
15079078 H.Zhang, B.Tweel, and L.Tong (2004).
Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop.
  Proc Natl Acad Sci U S A, 101, 5910-5915.
PDB codes: 1uyr 1uys 1uyt 1uyv
14993673 S.Kondo, Y.Nakajima, S.Sugio, J.Yong-Biao, S.Sueda, and H.Kondo (2004).
Structure of the biotin carboxylase subunit of pyruvate carboxylase from Aquifex aeolicus at 2.2 A resolution.
  Acta Crystallogr D Biol Crystallogr, 60, 486-492.
PDB code: 1ulz
15090492 T.Kanamori, N.Kanou, H.Atomi, and T.Imanaka (2004).
Enzymatic characterization of a prokaryotic urea carboxylase.
  J Bacteriol, 186, 2532-2539.  
15215578 Y.Sasaki, and Y.Nagano (2004).
Plant acetyl-CoA carboxylase: structure, biosynthesis, regulation, and gene manipulation for plant breeding.
  Biosci Biotechnol Biochem, 68, 1175-1184.  
15610732 Y.Shen, S.L.Volrath, S.C.Weatherly, T.D.Elich, and L.Tong (2004).
A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product.
  Mol Cell, 16, 881-891.
PDB codes: 1w93 1w96
15286736 Y.Shi, and P.Burn (2004).
Lipid metabolic enzymes: emerging drug targets for the treatment of obesity.
  Nat Rev Drug Discov, 3, 695-710.  
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
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.

 

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