5CTC

Humanized yeast ACC carboxyltransferase domain bound to tert-butyl 7-[(7-methyl-1H-indazol-5-yl)carbonyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of spirocyclic-diamine inhibitors of mammalian acetyl CoA-carboxylase.

Kung, D.W.Griffith, D.A.Esler, W.P.Vajdos, F.F.Mathiowetz, A.M.Doran, S.D.Amor, P.A.Bagley, S.W.Banks, T.Cabral, S.Ford, K.Garcia-Irizarry, C.N.Landis, M.S.Loomis, K.McPherson, K.Niosi, M.Rockwell, K.L.Rose, C.Smith, A.C.Southers, J.A.Tapley, S.Tu, M.Valentine, J.J.

(2015) Bioorg Med Chem Lett 25: 5352-5356

  • DOI: https://doi.org/10.1016/j.bmcl.2015.09.035
  • Primary Citation of Related Structures:  
    5CTB, 5CTC, 5CTE

  • PubMed Abstract: 

    A novel series of spirocyclic-diamine based, isoform non-selective inhibitors of acetyl-CoA carboxylase (ACC) is described. These spirodiamine derivatives were discovered by design of a library to mimic the structural rigidity and hydrogen-bonding pattern observed in the co-crystal structure of spirochromanone inhibitor I. The lead compound 3.5.1 inhibited de novo lipogenesis in rat hepatocytes, with an IC50 of 0.30 μM.


  • Organizational Affiliation

    Worldwide Medicinal Chemistry, Groton, CT 06340, United States. Electronic address: daniel.w.kung@pfizer.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): 9 
Gene Names: ACC1ABP2FAS3MTR7YNR016CN3175
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 247.272α = 90
b = 122.705β = 94.3
c = 146.429γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2015-10-14 
  • Deposition Author(s): Vajdos, F.F.

Revision History  (Full details and data files)

  • Version 1.0: 2015-10-14
    Type: Initial release
  • Version 1.1: 2015-11-11
    Changes: Database references
  • Version 1.2: 2024-03-06
    Changes: Data collection, Database references, Derived calculations