2ABJ

Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases.

Hu, L.Y.Boxer, P.A.Kesten, S.R.Lei, H.J.Wustrow, D.J.Moreland, D.W.Zhang, L.Ahn, K.Ryder, T.R.Liu, X.Rubin, J.R.Fahnoe, K.Carroll, R.T.Dutta, S.Fahnoe, D.C.Probert, A.W.Roof, R.L.Rafferty, M.F.Kostlan, C.R.Scholten, J.D.Hood, M.Ren, X.D.Schielke, G.P.Su, T.Z.Taylor, C.P.Mistry, A.McConnell, P.Hasemann, C.Ohren, J.

(2006) Bioorg Med Chem Lett 16: 2337-2340

  • DOI: https://doi.org/10.1016/j.bmcl.2005.07.058
  • Primary Citation of Related Structures:  
    2ABJ

  • PubMed Abstract: 

    The inhibition of the cytosolic isoenzyme BCAT that is expressed specifically in neuronal tissue is likely to be useful for the treatment of neurodegenerative and other neurological disorders where glutamatergic mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 microM in the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are described.


  • Organizational Affiliation

    Pfizer Global Research and Development, Ann Arbor, MI, USA. Lain-Yen.Hu@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Branched-chain-amino-acid aminotransferase, cytosolicA,
B [auth D],
C [auth G],
D [auth J]
366Homo sapiensMutation(s): 5 
Gene Names: BCAT1BCT1ECA39
EC: 2.6.1.42
UniProt & NIH Common Fund Data Resources
Find proteins for P54687 (Homo sapiens)
Explore P54687 
Go to UniProtKB:  P54687
PHAROS:  P54687
GTEx:  ENSG00000060982 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP54687
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
CBC Binding MOAD:  2ABJ IC50: 800 (nM) from 1 assay(s)
BindingDB:  2ABJ IC50: 230 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.327α = 90
b = 114.517β = 90
c = 148.869γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-06-27
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description