1THR

STRUCTURES OF THROMBIN COMPLEXES WITH A DESIGNED AND A NATURAL EXOSITE INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Observed: 0.155 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structures of thrombin complexes with a designed and a natural exosite peptide inhibitor.

Qiu, X.Yin, M.Padmanabhan, K.P.Krstenansky, J.L.Tulinsky, A.

(1993) J Biol Chem 268: 20318-20326

  • Primary Citation of Related Structures:  
    1THR, 1THS

  • PubMed Abstract: 

    The structures of two hirudin-based fibrinogen recognition exosite peptide inhibitors with significantly different sequences complexed with alpha-thrombin at a site distinct from the active site (exosite) have been determined crystallographically at 2.2 and 2.3 A resolution. One is a designed synthetic peptide with some nonconventional amino acid residues (MDL-28050), and the other is a natural COOH-terminal peptide isolated from the leech Hirudinaria manillensis (hirullin P18). The structures have been refined by restrained least squares methods to R values of 0.161 and 0.155, respectively. The first stretch of each peptide, corresponding to hirudin 55-59, associates with thrombin similar to hirudin and hirugen (hirudin 53-64). Although the remaining residues of the inhibitors interact with and bind to thrombin, the binding is accomplished. through a rigid body conformational adjustment of the peptide with respect to the conformation displayed by hirudin and hirugen (40 degrees rotation about the Ile59, CA-C bond). This causes the side groups of cyclohexylalanine 64' of MDL-28050 and Ile60, of hirullin to point in the opposite direction of the all important Tyr63, ring of hirudin and hirugen but permits the residues to penetrate and interact with the 3(10) turn hydrophobic binding pocket of thrombin. Thus, the hydrophobic interaction is accomplished in a different way by virtue of the substrate conformational readjustment. The results show that the first stretch of peptide makes concerted and efficient binding interactions with thrombin, and the peptide positions of the inhibitors are fairly specific and homologous so that the stretch appears to be related to specific recognition associated with the exosite. The relative flexibility of structure and sequence of the second stretch is a display of tolerance of imprecision by thrombin in its COOH-terminal hydrophobic association with hirudin-based inhibitors.


  • Organizational Affiliation

    Department of Chemistry, Michigan State University, East Lansing 48824-1322.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
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)
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
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 
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: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HIRULLINC [auth I]13Hirudinaria manillensisMutation(s): 0 
UniProt
Find proteins for P26631 (Hirudinaria manillensis)
Explore P26631 
Go to UniProtKB:  P26631
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26631
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Observed: 0.155 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.43α = 90
b = 72.32β = 100.55
c = 72.81γ = 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: 1994-01-31
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other
  • Version 1.4: 2013-03-13
    Changes: Other
  • Version 1.5: 2024-06-05
    Changes: Data collection, Database references, Other