PDBsum entry 1dv2

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protein ligands Protein-protein interface(s) links
Ligase PDB id
Protein chains
450 a.a. *
ATP ×2
Waters ×130
* Residue conservation analysis
PDB id:
Name: Ligase
Title: The structure of biotin carboxylase, mutant e288k, complexed with atp
Structure: Biotin carboxylase. Chain: a, b. Fragment: biotin carboxylase. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.172     R-free:   0.203
Authors: J.B.Thoden,C.Z.Blanchard,H.M.Holden,G.L.Waldrop
Key ref:
J.B.Thoden et al. (2000). Movement of the biotin carboxylase B-domain as a result of ATP binding. J Biol Chem, 275, 16183-16190. PubMed id: 10821865 DOI: 10.1074/jbc.275.21.16183
19-Jan-00     Release date:   09-Jun-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P24182  (ACCC_ECOLI) -  Biotin carboxylase
449 a.a.
450 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - Biotin carboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + biotin-[carboxyl-carrier-protein] + CO2 = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein]
Bound ligand (Het Group name = ATP)
corresponds exactly
+ biotin-[carboxyl-carrier-protein]
+ CO(2)
+ phosphate
+ carboxy-biotin-[carboxyl-carrier-protein]
   Enzyme class 2: E.C.  - Acetyl-CoA carboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + acetyl-CoA + HCO3- = ADP + phosphate + malonyl-CoA
Bound ligand (Het Group name = ATP)
corresponds exactly
+ acetyl-CoA
+ HCO(3)(-)
+ phosphate
+ malonyl-CoA
      Cofactor: 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   6 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1074/jbc.275.21.16183 J Biol Chem 275:16183-16190 (2000)
PubMed id: 10821865  
Movement of the biotin carboxylase B-domain as a result of ATP binding.
J.B.Thoden, C.Z.Blanchard, H.M.Holden, G.L.Waldrop.
Acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis. In Escherichia coli, the enzyme is composed of three distinct protein components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. The biotin carboxylase component has served for many years as a paradigm for mechanistic studies devoted toward understanding more complicated biotin-dependent carboxylases. The three-dimensional x-ray structure of an unliganded form of E. coli biotin carboxylase was originally solved in 1994 to 2.4-A resolution. This study revealed the architecture of the enzyme and demonstrated that the protein belongs to the ATP-grasp superfamily. Here we describe the three-dimensional structure of the E. coli biotin carboxylase complexed with ATP and determined to 2.5-A resolution. The major conformational change that occurs upon nucleotide binding is a rotation of approximately 45(o) of one domain relative to the other domains thereby closing off the active site pocket. Key residues involved in binding the nucleotide to the protein include Lys-116, His-236, and Glu-201. The backbone amide groups of Gly-165 and Gly-166 participate in hydrogen bonding interactions with the phosphoryl oxygens of the nucleotide. A comparison of this closed form of biotin carboxylase with carbamoyl-phosphate synthetase is presented.
  Selected figure(s)  
Figure 2.
Fig. 2. Mode of binding of the inorganic phosphate ion to biotin carboxylase. Shown in a is a representative portion of the electron density map near the phosphate. The map, contoured at 1 , was calculated with coefficients of the form (2F[o] F[c]), where F[o] was the native structure factor amplitude and F[c] was the calculated structure factor amplitude. The hydrogen bonding pattern around the phosphate ion is indicated by the dashed lines in b. Water molecules are depicted as red spheres.
Figure 5.
Fig. 5. Superposition of the -carbon trace of native biotin carboxylase onto that of the E288K protein/ATP complex. The unliganded form of biotin carboxylase is shown in red bonds, while the E288K protein is displayed in black bonds. The ATP is depicted in a ball-and-stick representation.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 16183-16190) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21120858 B.R.Novak, D.Moldovan, G.L.Waldrop, and Queiroz (2011).
Behavior of the ATP grasp domain of biotin carboxylase monomers and dimers studied using molecular dynamics simulations.
  Proteins, 79, 622-632.  
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
20361049 J.O.Wrabl, and V.J.Hilser (2010).
Investigating homology between proteins using energetic profiles.
  PLoS Comput Biol, 6, e1000722.  
20045436 P.K.Fyfe, M.S.Alphey, and W.N.Hunter (2010).
Structure of Trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme.
  Mol Biochem Parasitol, 170, 93-99.
PDB code: 2wyo
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
19497730 J.Matsui, J.Nagano, D.Miyoshi, K.Tamaki, and N.Sugimoto (2009).
An approach to peptide-based ATP receptors by a combination of random selection, rational design, and molecular imprinting.
  Biosens Bioelectron, 25, 563-567.  
18725455 I.Mochalkin, J.R.Miller, A.Evdokimov, S.Lightle, C.Yan, C.K.Stover, and G.L.Waldrop (2008).
Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase.
  Protein Sci, 17, 1706-1718.
PDB codes: 2c00 2j9g 2vpq 2vqd 2vr1
18460546 R.Mosca, and T.R.Schneider (2008).
RAPIDO: a web server for the alignment of protein structures in the presence of conformational changes.
  Nucleic Acids Res, 36, W42-W46.  
18613815 S.Jitrapakdee, M.St Maurice, I.Rayment, W.W.Cleland, J.C.Wallace, and P.V.Attwood (2008).
Structure, mechanism and regulation of pyruvate carboxylase.
  Biochem J, 413, 369-387.  
18271571 S.O.Nilsson Lill, J.Gao, and G.L.Waldrop (2008).
Molecular dynamics simulations of biotin carboxylase.
  J Phys Chem B, 112, 3149-3156.  
18297087 S.Xiang, and L.Tong (2008).
Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.
  Nat Struct Mol Biol, 15, 295-302.
PDB codes: 3bg3 3bg5 3bg9
17876819 Y.S.Cho, J.I.Lee, D.Shin, H.T.Kim, Y.H.Cheon, C.I.Seo, Y.E.Kim, Y.L.Hyun, Y.S.Lee, K.Sugiyama, S.Y.Park, S.Ro, J.M.Cho, T.G.Lee, and Y.S.Heo (2008).
Crystal structure of the biotin carboxylase domain of human acetyl-CoA carboxylase 2.
  Proteins, 70, 268-272.
PDB code: 2hjw
17717183 M.St Maurice, L.Reinhardt, K.H.Surinya, P.V.Attwood, J.C.Wallace, W.W.Cleland, and I.Rayment (2007).
Domain architecture of pyruvate carboxylase, a biotin-dependent multifunctional enzyme.
  Science, 317, 1076-1079.
PDB code: 2qf7
17659996 S.Jitrapakdee, K.H.Surinya, A.Adina-Zada, S.W.Polyak, C.Stojkoski, R.Smyth, G.W.Booker, W.W.Cleland, P.V.Attwood, and J.C.Wallace (2007).
Conserved Glu40 and Glu433 of the biotin carboxylase domain of yeast pyruvate carboxylase I isoenzyme are essential for the association of tetramers.
  Int J Biochem Cell Biol, 39, 2120-2134.  
17642515 S.Kondo, Y.Nakajima, S.Sugio, S.Sueda, M.N.Islam, and H.Kondo (2007).
Structure of the biotin carboxylase domain of pyruvate carboxylase from Bacillus thermodenitrificans.
  Acta Crystallogr D Biol Crystallogr, 63, 885-890.
PDB code: 2dzd
17124497 C.H.Pai, B.Y.Chiang, T.P.Ko, C.C.Chou, C.M.Chong, F.J.Yen, S.Chen, J.K.Coward, A.H.Wang, and C.H.Lin (2006).
Dual binding sites for translocation catalysis by Escherichia coli glutathionylspermidine synthetase.
  EMBO J, 25, 5970-5982.
PDB codes: 2io7 2io8 2io9 2ioa 2iob
16983687 L.Tong, and H.J.Harwood (2006).
Acetyl-coenzyme A carboxylases: versatile targets for drug discovery.
  J Cell Biochem, 99, 1476-1488.  
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
16146579 D.M.Standley, H.Toh, and H.Nakamura (2005).
GASH: an improved algorithm for maximizing the number of equivalent residues between two protein structures.
  BMC Bioinformatics, 6, 221.  
15725057 K.Izui, H.Matsumura, T.Furumoto, and Y.Kai (2004).
Phosphoenolpyruvate carboxylase: a new era of structural biology.
  Annu Rev Plant Biol, 55, 69-84.  
15359379 M.R.Baumgartner, M.F.Dantas, T.Suormala, S.Almashanu, C.Giunta, D.Friebel, B.Gebhardt, B.Fowler, G.F.Hoffmann, E.R.Baumgartner, and D.Valle (2004).
Isolated 3-methylcrotonyl-CoA carboxylase deficiency: evidence for an allele-specific dominant negative effect and responsiveness to biotin therapy.
  Am J Hum Genet, 75, 790-800.  
  15043388 R.J.Heath, and C.O.Rock (2004).
Fatty acid biosynthesis as a target for novel antibacterials.
  Curr Opin Investig Drugs, 5, 146-153.  
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
15030490 S.Sueda, M.N.Islam, and H.Kondo (2004).
Protein engineering of pyruvate carboxylase: investigation on the function of acetyl-CoA and the quaternary structure.
  Eur J Biochem, 271, 1391-1400.  
15090492 T.Kanamori, N.Kanou, H.Atomi, and T.Imanaka (2004).
Enzymatic characterization of a prokaryotic urea carboxylase.
  J Bacteriol, 186, 2532-2539.  
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
12121720 J.E.Cronan, and G.L.Waldrop (2002).
Multi-subunit acetyl-CoA carboxylases.
  Prog Lipid Res, 41, 407-435.  
11544358 J.W.Campbell, and J.E.Cronan (2001).
Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery.
  Annu Rev Microbiol, 55, 305-332.  
11714930 L.H.Weaver, K.Kwon, D.Beckett, and B.W.Matthews (2001).
Competing protein:protein interactions are proposed to control the biological switch of the E coli biotin repressor.
  Protein Sci, 10, 2618-2622.
PDB codes: 1k67 1k69
11170888 M.E.Gallardo, L.R.Desviat, J.M.Rodríguez, J.Esparza-Gordillo, C.Pérez-Cerdá, B.Pérez, P.Rodríguez-Pombo, O.Criado, R.Sanz, D.H.Morton, K.M.Gibson, T.P.Le, A.Ribes, Córdoba, M.Ugarte, and M.A.Peñalva (2001).
The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism.
  Am J Hum Genet, 68, 334-346.  
11181649 M.R.Baumgartner, S.Almashanu, T.Suormala, C.Obie, R.N.Cole, S.Packman, E.R.Baumgartner, and D.Valle (2001).
The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.
  J Clin Invest, 107, 495-504.  
11591436 R.J.Heath, S.W.White, and C.O.Rock (2001).
Lipid biosynthesis as a target for antibacterial agents.
  Prog Lipid Res, 40, 467-497.  
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.