1JWT

CRYSTAL STRUCTURE OF THROMBIN IN COMPLEX WITH A NOVEL BICYCLIC LACTAM INHIBITOR

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.301 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.

Levesque, S., St-Denis, Y., Bachand, B., Preville, P., Leblond, L., Winocour, P.D., Edmunds, J.J., Rubin, J.R., Siddiqui, M.A.

(2001) Bioorg Med Chem Lett 11: 3161-3164

  • DOI: https://doi.org/10.1016/s0960-894x(01)00661-8
  • Primary Citation of Related Structures:  
    1JWT

  • PubMed Abstract: 

    Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the P1 residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo.

    • Organizational Affiliation: 

    Shire BioChem Inc., 275 Armand-Frappier Blvd., Laval, H7V 4A7, Québec, Canada. slevesque@ca.shire.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Prothrombin305Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BLI
Query on BLI
Download Ideal Coordinates CCD File 
B [auth A]4-OXO-2-PHENYLMETHANESULFONYL-OCTAHYDRO-PYRROLO[1,2-A]PYRAZINE-6-CARBOXYLIC ACID [1-(N-HYDROXYCARBAMIMIDOYL)-PIPERIDIN-4-YLMETHYL]-AMIDE
C22 H32 N6 O5 S
DHTSUHWLPAEEQB-OALUTQOASA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BLI Binding MOAD:  1JWT Ki: 14 (nM) from 1 assay(s)
PDBBind:  1JWT Ki: 14 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.301 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.54α = 90
b = 72.18β = 100.99
c = 73.41γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
AUTOMARdata reduction
X-PLORmodel building
X-PLORrefinement
XDSdata reduction
X-PLORphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-02-27
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description