PDBsum entry 2vr1

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Jmol PyMol
Protein chains
444 a.a. *
_CL ×2
Waters ×233
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of biotin carboxylase from e. Coli in complex with atp analog, adpcf2p.
Structure: Biotin carboxylase. Chain: a, b. Synonym: acetyl-coa carboxylase subunit a, acc. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
2.60Å     R-factor:   0.192     R-free:   0.247
Authors: I.Mochalkin,G.L.Waldrop
Key ref:
I.Mochalkin et al. (2008). Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase. Protein Sci, 17, 1706-1718. PubMed id: 18725455 DOI: 10.1110/ps.035584.108
24-Mar-08     Release date:   09-Sep-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P24182  (ACCC_ECOLI) -  Biotin carboxylase
449 a.a.
444 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Biotin carboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + biotin-[carboxyl-carrier-protein] + HCO3- = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-protein]
+ biotin-[carboxyl-carrier-protein]
+ HCO(3)(-)
Bound ligand (Het Group name = ATF)
matches with 76.47% similarity
+ 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
+ acetyl-CoA
+ HCO(3)(-)
Bound ligand (Het Group name = ATF)
matches with 76.47% similarity
+ 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   2 terms 
  Biological process     malonyl-CoA biosynthetic process   5 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1110/ps.035584.108 Protein Sci 17:1706-1718 (2008)
PubMed id: 18725455  
Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase.
I.Mochalkin, J.R.Miller, A.Evdokimov, S.Lightle, C.Yan, C.K.Stover, G.L.Waldrop.
Bacterial acetyl-CoA carboxylase is a multifunctional biotin-dependent enzyme that consists of three separate proteins: biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT). Acetyl-CoA carboxylase is a potentially attractive target for novel antibiotics because it catalyzes the first committed step in fatty acid biosynthesis. In the first half-reaction, BC catalyzes the ATP-dependent carboxylation of BCCP. In the second half-reaction, the carboxyl group is transferred from carboxybiotinylated BCCP to acetyl-CoA to produce malonyl-CoA. A series of structures of BC from several bacteria crystallized in the presence of various ATP analogs is described that addresses three major questions concerning the catalytic mechanism. The structure of BC bound to AMPPNP and the two catalytically essential magnesium ions resolves inconsistencies between the kinetics of active-site BC mutants and previously reported BC structures. Another structure of AMPPNP bound to BC shows the polyphosphate chain folded back on itself, and not in the correct (i.e., extended) conformation for catalysis. This provides the first structural evidence for the hypothesis of substrate-induced synergism, which posits that ATP binds nonproductively to BC in the absence of biotin. The BC homodimer has been proposed to exhibit half-sites reactivity where the active sites alternate or "flip-flop" their catalytic cycles. A crystal structure of BC showed the ATP analog AMPPCF(2)P bound to one subunit while the other subunit was unliganded. The liganded subunit was in the closed or catalytic conformation while the unliganded subunit was in the open conformation. This provides the first structural evidence for half-sites reactivity in BC.
  Selected figure(s)  
Figure 4.
Figure 4. Stereoview of superimposed AMPPNP in SaBC and EcBC crystal structures. SaBC/AMPPNP structure is colored in red. EcBC/AMPPNP structure is colored in blue. SaBC residues involved in interactions with the ligand are shown in sticks with the following atom colors: carbon, yellow; nitrogen, blue; oxygen, red. Images were prepared using PyMOL molecular graphics systems (DeLano Scientific).
Figure 5.
Figure 5. View of octahedrally coordinated magnesium ions in BC crystal structures. Nucleotide molecules and protein residues are shown in sticks with the following atom colors: carbon, green; nitrogen, blue; oxygen, red; phosphorus, orange. Magnesium ions and water molecules are shown as green and red spheres. (A) View of two magnesium-binding sites in the SaBC/AMPPNP structure. (B) View of one magnesium-binding site in the PaBC/AMPCP structure.
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2008, 17, 1706-1718) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21426897 A.Adina-Zada, R.Hazra, C.Sereeruk, S.Jitrapakdee, T.N.Zeczycki, M.S.Maurice, W.W.Cleland, J.C.Wallace, and P.V.Attwood (2011).
Probing the allosteric activation of pyruvate carboxylase using 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate as a fluorescent mimic of the allosteric activator acetyl CoA.
  Arch Biochem Biophys, 509, 117-126.  
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.  
21097780 U.Pieper, B.M.Webb, D.T.Barkan, D.Schneidman-Duhovny, A.Schlessinger, H.Braberg, Z.Yang, E.C.Meng, E.F.Pettersen, C.C.Huang, R.S.Datta, P.Sampathkumar, M.S.Madhusudhan, K.Sjölander, T.E.Ferrin, S.K.Burley, and A.Sali (2011).
ModBase, a database of annotated comparative protein structure models, and associated resources.
  Nucleic Acids Res, 39, D465-D474.  
19193851 C.T.Walsh, and M.A.Fischbach (2009).
Repurposing libraries of eukaryotic protein kinase inhibitors for antibiotic discovery.
  Proc Natl Acad Sci U S A, 106, 1689-1690.  
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
19164768 J.R.Miller, S.Dunham, I.Mochalkin, C.Banotai, M.Bowman, S.Buist, B.Dunkle, D.Hanna, H.J.Harwood, M.D.Huband, A.Karnovsky, M.Kuhn, C.Limberakis, J.Y.Liu, S.Mehrens, W.T.Mueller, L.Narasimhan, A.Ogden, J.Ohren, J.V.Prasad, J.A.Shelly, L.Skerlos, M.Sulavik, V.H.Thomas, S.VanderRoest, L.Wang, Z.Wang, A.Whitton, T.Zhu, and C.K.Stover (2009).
A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore.
  Proc Natl Acad Sci U S A, 106, 1737-1742.
PDB codes: 2v58 2v59 2v5a
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.