1AVG

THROMBIN INHIBITOR FROM TRIATOMA PALLIDIPENNIS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug.

Fuentes-Prior, P.Noeske-Jungblut, C.Donner, P.Schleuning, W.D.Huber, R.Bode, W.

(1997) Proc Natl Acad Sci U S A 94: 11845-11850

  • DOI: https://doi.org/10.1073/pnas.94.22.11845
  • Primary Citation of Related Structures:  
    1AVG

  • PubMed Abstract: 

    Triabin, a 142-residue protein from the saliva of the blood-sucking triatomine bug Triatoma pallidipennis, is a potent and selective thrombin inhibitor. Its stoichiometric complex with bovine alpha-thrombin was crystallized, and its crystal structure was solved by Patterson search methods and refined at 2.6-A resolution to an R value of 0.184. The analysis revealed that triabin is a compact one-domain molecule essentially consisting of an eight-stranded beta-barrel. The eight strands A to H are arranged in the order A-C-B-D-E-F-G-H, with the first four strands exhibiting a hitherto unobserved up-up-down-down topology. Except for the B-C inversion, the triabin fold exhibits the regular up-and-down topology of lipocalins. In contrast to the typical ligand-binding lipocalins, however, the triabin barrel encloses a hydrophobic core intersected by a unique salt-bridge cluster. Triabin interacts with thrombin exclusively via its fibrinogen-recognition exosite. Surprisingly, most of the interface interactions are hydrophobic. A prominent exception represents thrombin's Arg-77A side chain, which extends into a hydrophobic triabin pocket forming partially buried salt bridges with Glu-128 and Asp-135 of the inhibitor. The fully accessible active site of thrombin in this complex is in agreement with its retained hydrolytic activity toward small chromogenic substrates. Impairment of thrombin's fibrinogen converting activity or of its thrombomodulin-mediated protein C activation capacity upon triabin binding is explained by usage of overlapping interaction sites of fibrinogen, thrombomodulin, and triabin on thrombin. These data demonstrate that triabin inhibits thrombin via a novel and unique mechanism that might be of interest in the context of potential therapeutic applications.


  • Organizational Affiliation

    Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, D-82152 Martinsried, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THROMBINA [auth L]41Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
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Go to UniProtKB:  P00735
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UniProt GroupP00735
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
THROMBINB [auth H]259Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
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Go to UniProtKB:  P00735
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UniProt GroupP00735
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
TRIABINC [auth I]142Meccus pallidipennisMutation(s): 0 
UniProt
Find proteins for Q27049 (Meccus pallidipennis)
Explore Q27049 
Go to UniProtKB:  Q27049
Entity Groups  
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UniProt GroupQ27049
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.84α = 90
b = 67.23β = 90
c = 183.49γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
ROTAVATAdata reduction
AGROVATAdata reduction
AMoREphasing
X-PLORrefinement
CCP4data scaling
ROTAVATA)data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-12-30
    Type: Initial release
  • Version 1.1: 2008-03-25
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance