2A1D

Staphylocoagulase bound to bovine thrombin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.233 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Structural Basis for Reduced Staphylocoagulase-mediated Bovine Prothrombin Activation

Friedrich, R.Panizzi, P.Kawabata, S.Bode, W.Bock, P.E.Fuentes-Prior, P.

(2006) J Biol Chem 281: 1188-1195

  • DOI: https://doi.org/10.1074/jbc.M507957200
  • Primary Citation of Related Structures:  
    2A1D

  • PubMed Abstract: 

    Staphylocoagulase (SC) is a protein secreted by the human pathogen, Staphylococcus aureus, that activates human prothrombin (ProT) by inducing a conformational change. SC-bound ProT efficiently clots fibrinogen, thus bypassing the physiological blood coagulation pathway. The crystal structure of a fully active SC fragment, SC-(1-325), bound to human prethrombin 2 showed that the SC-(1-325) N terminus inserts into the Ile(16) pocket of prethrombin 2, thereby inducing expression of a functional catalytic site in the cognate zymogen without peptide bond cleavage. As shown here, SC-(1-325) binds to bovine and human ProT with similar affinity but activates the bovine zymogen only very poorly. By contrast to the approximately 2-fold difference in chromogenic substrate kinetic constants between human thrombin and the SC-(1-325).human (pro)thrombin complexes, SC-(1-325).bovine ProT shows a 3,500-fold lower k(cat)/K(m) compared with free bovine thrombin, because of a 47-fold increase in K(m) and a 67-fold decrease in k(cat). The SC-(1-325).bovine ProT complex is approximately 5,800-fold less active compared with its human counterpart. Comparison of human and bovine fibrinogen as substrates of human and bovine thrombin and the SC-(1-325).(pro)thrombin complexes indicates that the species specificity of SC-(1-325) cofactor activity is determined primarily by differences in conformational activation of bound ProT. These results suggest that the catalytic site in the SC-(1-325).bovine ProT complex is incompletely formed. The current crystal structure of SC-(1-325).bovine thrombin reveals that SC would dock similarly to the bovine proenzyme, whereas the bovine (pro)thrombin-characteristic residues Arg(144) and Arg(145) would likely interfere with insertion of the SC N terminus, thus explaining the greatly reduced activation of bovine ProT.


  • Organizational Affiliation

    Proteinase Research Group, Max Planck Institute of Biochemistry, Martinsried, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
thrombinA,
D [auth E]
41Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
Explore P00735 
Go to UniProtKB:  P00735
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00735
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
thrombinB,
E [auth F]
259Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
Explore P00735 
Go to UniProtKB:  P00735
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00735
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
StaphylocoagulaseC [auth D],
F [auth H]
329Staphylococcus aureusMutation(s): 0 
UniProt
Find proteins for P17855 (Staphylococcus aureus)
Explore P17855 
Go to UniProtKB:  P17855
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP17855
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0G6
Query on 0G6

Download Ideal Coordinates CCD File 
G [auth B],
J [auth F]
D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide
C21 H34 Cl N6 O3
DVFLYEYCMMLBTQ-VSZNYVQBSA-O
NAG
Query on NAG

Download Ideal Coordinates CCD File 
H [auth B]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
NA
Query on NA

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I [auth B],
K [auth F]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 4
IDChains NameType/Class2D Diagram3D Interactions
PRD_000020 (0G6)
Query on PRD_000020
G [auth B],
J [auth F]
D-Phe-Pro-Arg-CH2ClPeptide-like / Inhibitor
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.233 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 183.78α = 90
b = 102.54β = 129.14
c = 134.04γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
TRUNCATEdata reduction
AMoREphasing
CNSrefinement
CCP4data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-09-27
    Type: Initial release
  • Version 1.1: 2008-04-30
    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: 2013-02-27
    Changes: Other
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2024-03-20
    Changes: Advisory, Data collection, Database references, Source and taxonomy, Structure summary