4WXI

FACTOR XIA IN COMPLEX WITH THE INHIBITOR trans-N-{(1S)-1-[4-(3-amino-2H-indazol-6-yl)pyridin-2-yl]-2-phenylethyl}-4-(aminomethyl)cyclohexanecarboxamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Pyridine and pyridinone-based factor XIa inhibitors.

Corte, J.R.Fang, T.Hangeland, J.J.Friends, T.J.Rendina, A.R.Luettgen, J.M.Bozarth, J.M.Barbera, F.A.Rossi, K.A.Wei, A.Ramamurthy, V.Morin, P.E.Seiffert, D.A.Wexler, R.R.Quan, M.L.

(2015) Bioorg Med Chem Lett 25: 925-930

  • DOI: https://doi.org/10.1016/j.bmcl.2014.12.050
  • Primary Citation of Related Structures:  
    4WXI

  • PubMed Abstract: 

    The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (±)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.


  • Organizational Affiliation

    Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States. Electronic address: james.corte@bms.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
COAGULATION FACTOR XI, LIGHT CHAIN244Homo sapiensMutation(s): 2 
Gene Names: F11
EC: 3.4.21.27
UniProt & NIH Common Fund Data Resources
Find proteins for P03951 (Homo sapiens)
Explore P03951 
Go to UniProtKB:  P03951
PHAROS:  P03951
GTEx:  ENSG00000088926 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03951
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.180 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79α = 90
b = 79β = 90
c = 106.5γ = 120
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2015-01-28 
  • Deposition Author(s): Wei, A.

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-28
    Type: Initial release
  • Version 1.1: 2015-02-11
    Changes: Database references
  • Version 1.2: 2015-02-18
    Changes: Database references
  • Version 1.3: 2018-08-29
    Changes: Data collection, Derived calculations, Source and taxonomy, Structure summary