3TDC

Crystal Structure of Human Acetyl-CoA carboxylase 2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors.

Yamashita, T.Kamata, M.Endo, S.Yamamoto, M.Kakegawa, K.Watanabe, H.Miwa, K.Yamano, T.Funata, M.Sakamoto, J.Tani, A.Mol, C.D.Zou, H.Dougan, D.R.Sang, B.Snell, G.Fukatsu, K.

(2011) Bioorg Med Chem Lett 21: 6314-6318

  • DOI: https://doi.org/10.1016/j.bmcl.2011.08.117
  • Primary Citation of Related Structures:  
    3TDC

  • PubMed Abstract: 

    The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety.


  • Organizational Affiliation

    Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. Yamashita_Tohru@takeda.co.jp


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acetyl-CoA carboxylase 2 variant762Homo sapiensMutation(s): 0 
EC: 6.4.1.2
UniProt & NIH Common Fund Data Resources
Find proteins for O00763 (Homo sapiens)
Explore O00763 
Go to UniProtKB:  O00763
PHAROS:  O00763
GTEx:  ENSG00000076555 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00763
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0EU
Query on 0EU

Download Ideal Coordinates CCD File 
B [auth A]1-[3-({4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-7-azaspiro[4.5]dec-7-yl]piperidin-1-yl}carbonyl)-1-benzothiophen-2-yl]-3-ethylurea
C27 H36 N4 O4 S
DSUNZEZCXUMUEH-MHZLTWQESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0EU PDBBind:  3TDC IC50: 5.4 (nM) from 1 assay(s)
BindingDB:  3TDC IC50: min: 5.4, max: 13 (nM) from 2 assay(s)
Binding MOAD:  3TDC IC50: 5.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.172 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.921α = 90
b = 119.756β = 90
c = 146.035γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
DENZOdata reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-12
    Type: Initial release
  • Version 1.1: 2011-11-16
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description