1NU7

Staphylocoagulase-Thrombin Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation

Friedrich, R.Panizzi, P.Fuentes-Prior, P.Richter, K.Verhamme, I.Anderson, P.J.Kawabata, S.Huber, R.Bode, W.Bock, P.E.

(2003) Nature 425: 535-539

  • DOI: https://doi.org/10.1038/nature01962
  • Primary Citation of Related Structures:  
    1NU7, 1NU9

  • PubMed Abstract: 

    Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.


  • Organizational Affiliation

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


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thrombin light chainA,
D [auth E]
28Homo 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
Thrombin heavy chainB,
E [auth F]
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
StaphylocoagulaseC [auth D],
F [auth H]
282Staphylococcus aureusMutation(s): 0 
UniProt
Find proteins for Q846V4 (Staphylococcus aureus)
Explore Q846V4 
Go to UniProtKB:  Q846V4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ846V4
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0ZJ
Query on 0ZJ

Download Ideal Coordinates CCD File 
G [auth B],
M [auth F]
N-(sulfanylacetyl)-D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide
C23 H36 Cl N6 O4 S
AZCCJYZROBVYNQ-ZSYWTGECSA-O
HG
Query on HG

Download Ideal Coordinates CCD File 
H [auth D],
I [auth D],
N [auth H],
O [auth H]
MERCURY (II) ION
Hg
BQPIGGFYSBELGY-UHFFFAOYSA-N
IMD
Query on IMD

Download Ideal Coordinates CCD File 
J [auth D]
K [auth D]
L [auth D]
P [auth H]
Q [auth H]
J [auth D],
K [auth D],
L [auth D],
P [auth H],
Q [auth H],
R [auth H]
IMIDAZOLE
C3 H5 N2
RAXXELZNTBOGNW-UHFFFAOYSA-O
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 180.17α = 90
b = 102β = 130.08
c = 135.3γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-10-07
    Type: Initial release
  • Version 1.1: 2008-01-08
    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: 2012-12-12
    Changes: Other