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PDBsum entry 3h0s
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protein ligands Protein-protein interface(s) links
Transferase PDB id
3h0s

 

 

 

 

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Contents
Protein chains
693 a.a. *
Ligands
SO4 ×3
B38 ×3
Waters ×2403
* Residue conservation analysis
PDB id:
3h0s
Name: Transferase
Title: Crystal structure of the carboxyltransferase domain of acetyl-coenzyme a carboxylase in complex with compound 7
Structure: Acetyl-coa carboxylase. Chain: a, b, c. Fragment: residues 1476-2233. Synonym: acc, biotin carboxylase. Engineered: yes
Source: Saccharomyces cerevisiae. Yeast. Organism_taxid: 4932. Gene: fas3, acc1, ynr016c, n3175. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.43Å     R-factor:   0.166     R-free:   0.218
Authors: F.Vajdos
Key ref: J.W.Corbett et al. (2010). Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2. Bioorg Med Chem Lett, 20, 2383-2388. PubMed id: 20219367
Date:
10-Apr-09     Release date:   07-Apr-10    
PROCHECK
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 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.
693 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]
 + 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
 + 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    
 
 
Bioorg Med Chem Lett 20:2383-2388 (2010)
PubMed id: 20219367  
 
 
Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2.
J.W.Corbett, K.D.Freeman-Cook, R.Elliott, F.Vajdos, F.Rajamohan, D.Kohls, E.Marr, H.Zhang, L.Tong, M.Tu, S.Murdande, S.D.Doran, J.A.Houser, W.Song, C.J.Jones, S.B.Coffey, L.Buzon, M.L.Minich, K.J.Dirico, S.Tapley, R.K.McPherson, E.Sugarman, H.J.Harwood, W.Esler.
 
  ABSTRACT  
 
Screening Pfizer's compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21515056 C.Bengtsson, S.Blaho, D.B.Saitton, K.Brickmann, J.Broddefalk, O.Davidsson, T.Drmota, R.Folmer, K.Hallberg, S.Hallén, R.Hovland, E.Isin, P.Johannesson, B.Kull, L.O.Larsson, L.Löfgren, K.E.Nilsson, T.Noeske, N.Oakes, A.T.Plowright, V.Schnecke, P.Ståhlberg, P.Sörme, H.Wan, E.Wellner, and L.Oster (2011).
Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats.
  Bioorg Med Chem, 19, 3039-3053.
PDB code: 2x24
20439761 J.Marjanovic, D.Chalupska, C.Patenode, A.Coster, E.Arnold, A.Ye, G.Anesi, Y.Lu, I.Okun, S.Tkachenko, R.Haselkorn, and P.Gornicki (2010).
Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity.
  Proc Natl Acad Sci U S A, 107, 9093-9098.  
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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