5CTE

Humanized yeast ACC carboxyltransferase domain bound to 2,2-dimethylpropyl (1S)-1-methyl-8-[(7-methyl-1H-indazol-5-yl)carbonyl]-2,8-diazaspiro[4.5]decane-2-carboxylate

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

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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 carboxylaseA [auth B],
B [auth C]		769Saccharomyces cerevisiaeMutation(s): 9 
Gene Names: ACC1, ABP2, FAS3, MTR7, YNR016C, N3175
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
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
57L
Query on 57L
Download Ideal Coordinates CCD File 
C [auth B],
D [auth C]		2,2-dimethylpropyl (1S)-1-methyl-8-[(7-methyl-1H-indazol-5-yl)carbonyl]-2,8-diazaspiro[4.5]decane-2-carboxylate
C24 H34 N4 O3
ZOGULHIZBGRKQX-KRWDZBQOSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
E [auth C]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.34α = 90
b = 138.12β = 90
c = 185.55γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


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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