3H0Q

Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with compound 3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.205 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2.

Corbett, J.W.Freeman-Cook, K.D.Elliott, R.Vajdos, F.Rajamohan, F.Kohls, D.Marr, E.Zhang, H.Tong, L.Tu, M.Murdande, S.Doran, S.D.Houser, J.A.Song, W.Jones, C.J.Coffey, S.B.Buzon, L.Minich, M.L.Dirico, K.J.Tapley, S.McPherson, R.K.Sugarman, E.Harwood, H.J.Esler, W.

(2010) Bioorg Med Chem Lett 20: 2383-2388

  • DOI: https://doi.org/10.1016/j.bmcl.2009.04.091
  • Primary Citation of Related Structures:  
    3H0J, 3H0Q, 3H0S

  • PubMed 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.


  • Organizational Affiliation

    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. jmc1983mac@gmail.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acetyl-CoA carboxylase
A, B, C
769Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: FAS3ACC1YNR016CN3175
EC: 6.4.1.2 (PDB Primary Data), 6.3.4.14 (PDB Primary Data)
UniProt
Find proteins for Q00955 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore Q00955 
Go to UniProtKB:  Q00955
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00955
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
B37 PDBBind:  3H0Q IC50: 842 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.205 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 246.953α = 90
b = 124.248β = 94.229
c = 145.271γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations