3HAT

ACTIVE SITE MIMETIC INHIBITION OF THROMBIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Observed: 0.140 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Active-site mimetic inhibition of thrombin.

Mathews, I.I.Tulinsky, A.

(1995) Acta Crystallogr D Biol Crystallogr 51: 550-559

  • DOI: https://doi.org/10.1107/S0907444994013132
  • Primary Citation of Related Structures:  
    1FPC, 3HAT

  • PubMed Abstract: 

    The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed.


  • Organizational Affiliation

    Department of Chemistry, Michigan State University, East Lansing 48824, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ALPHA-THROMBIN (SMALL SUBUNIT)A [auth L]36Homo sapiensMutation(s): 0 
EC: 3.4.21.5
UniProt & NIH Common Fund Data Resources
Find proteins for P00734 (Homo sapiens)
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Go to UniProtKB:  P00734
PHAROS:  P00734
GTEx:  ENSG00000180210 
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UniProt GroupP00734
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ALPHA-THROMBIN (LARGE SUBUNIT)B [auth H]259Homo 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 
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UniProt GroupP00734
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HIRUGENC [auth I]12Hirudo medicinalisMutation(s): 0 
UniProt
Find proteins for P09945 (Hirudo medicinalis)
Explore P09945 
Go to UniProtKB:  P09945
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UniProt GroupP09945
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  • Reference Sequence

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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
FPAM (FIBRINOPEPTIDE A MIMIC)D [auth T]6N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TYS
Query on TYS
C [auth I]L-PEPTIDE LINKINGC9 H11 N O6 STYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Observed: 0.140 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.1α = 90
b = 72.4β = 101
c = 73γ = 90
Software Package:
Software NamePurpose
PROLSQrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-02-27
    Type: Initial release
  • Version 1.1: 2008-05-22
    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