1ZGV

Thrombin in complex with an oxazolopyridine inhibitor 2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization.

Deng, J.Z.McMasters, D.R.Rabbat, P.M.Williams, P.D.Coburn, C.A.Yan, Y.Kuo, L.C.Lewis, S.D.Lucas, B.J.Krueger, J.A.Strulovici, B.Vacca, J.P.Lyle, T.A.Burgey, C.S.

(2005) Bioorg Med Chem Lett 15: 4411-4416

  • DOI: https://doi.org/10.1016/j.bmcl.2005.07.022
  • Primary Citation of Related Structures:  
    1ZGI, 1ZGV

  • PubMed Abstract: 

    Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thrombin287Homo sapiensMutation(s): 0 
EC: 3.4.21.5
UniProt & NIH Common Fund Data Resources
Find proteins for P00734 (Homo sapiens)
Explore P00734 
Go to UniProtKB:  P00734
PHAROS:  P00734
GTEx:  ENSG00000180210 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00734
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hirudin10Hirudo medicinalisMutation(s): 0 
UniProt
Find proteins for P01050 (Hirudo medicinalis)
Explore P01050 
Go to UniProtKB:  P01050
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01050
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
501
Query on 501

Download Ideal Coordinates CCD File 
C [auth A]N7-BUTYL-N2-(5-CHLORO-2-METHYLPHENYL)-5-METHYL[1,2,4]TRIAZOLO[1,5-A]PYRIMIDINE-2,7-DIAMINE
C17 H21 Cl N6
ZTYBIJUAAWLJNU-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TYS
Query on TYS
B
L-PEPTIDE LINKINGC9 H11 N O6 STYR
Binding Affinity Annotations 
IDSourceBinding Affinity
501 Binding MOAD:  1ZGV IC50: 1000 (nM) from 1 assay(s)
PDBBind:  1ZGV IC50: 1000 (nM) from 1 assay(s)
BindingDB:  1ZGV IC50: 1000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.34α = 90
b = 72.33β = 101.07
c = 73.02γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-09-27
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other
  • Version 1.4: 2013-03-13
    Changes: Other