1NT1

thrombin in complex with selective macrocyclic inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


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


Literature

Design and synthesis of potent and selective macrocyclic thrombin inhibitors

Nantermet, P.G., Barrow, J.C., Newton, C.L., Pellicore, J.M., Young, M., Lewis, S.D., Lucas, B.J., Krueger, J.A., McMasters, D.R., Yan, Y., Kuo, L.C., Vacca, J.P., Selnick, H.G.

(2003) Bioorg Med Chem Lett 13: 2781-2784

  • DOI: https://doi.org/10.1016/s0960-894x(03)00506-7
  • Primary Citation of Related Structures:  
    1NM6, 1NT1

  • PubMed Abstract: 

    A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. philippe_nanternet@merck.com


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

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HirudinB [auth H]11Hirudo medicinalisMutation(s): 0 
UniProt
Find proteins for P28504 (Hirudo medicinalis)
Explore P28504 
Go to UniProtKB:  P28504
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28504
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
T76
Query on T76
Download Ideal Coordinates CCD File 
C [auth A](6R,21AS)-17-CHLORO-6-CYCLOHEXYL-2,3,6,7,10,11,19,20-OCTAHYDRO-1H,5H-PYRROLO[1,2-K][1,4,8,11,14]BENZOXATETRAAZA-CYCLOHEPTADECINE-5,8,12,21(9H,13H,21AH)-TETRONE
C25 H33 Cl N4 O5
CNGULIMOMYJRBP-WMZHIEFXSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TYS
Query on TYS		B [auth H]L-PEPTIDE LINKINGC9 H11 N O6 STYR
Binding Affinity Annotations 
IDSourceBinding Affinity
T76 BindingDB:  1NT1 Ki: min: 0.4, max: 1.3 (nM) from 2 assay(s)
Binding MOAD:  1NT1 Ki: 1.3 (nM) from 1 assay(s)
PDBBind:  1NT1 Ki: 1.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.1α = 90
b = 72.1β = 100.9
c = 73.2γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-09-02
    Type: Initial release
  • Version 1.1: 2008-04-29
    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: 2017-10-11
    Changes: Refinement description