4DY0

Crystal structure of native protease nexin-1 with heparin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 2.2 of the entry. See complete history


Literature

Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a 2-step recognition mechanism.

Li, W.Huntington, J.A.

(2012) Blood 120: 459-467

  • DOI: https://doi.org/10.1182/blood-2012-03-415869
  • Primary Citation of Related Structures:  
    4DY0, 4DY7

  • PubMed Abstract: 

    Protease nexin-1 (PN1) is a specific and extremely efficient inhibitor of thrombin. However, unlike other thrombin inhibitors belonging to the serpin family, PN1 is not synthesized in the liver and does not circulate in the blood. Rather, PN1 is expressed by multiple cell types, including macrophages, smooth muscle cells, and platelets, and it is on the surface of these cells, bound to glycosaminoglycans, that PN1 inhibits the signaling functions of thrombin. PN1 sets the threshold for thrombin-induced platelet activation and has been implicated in atherosclerosis. However, in spite of the emerging importance of PN1 in thrombosis and atherosclerosis, little is know about how it associates to cells and how it inhibits thrombin at rates that surpass the diffusion limit. To address these issues, we determined the crystal structures of PN1 in complex with heparin, and in complex with catalytically inert thrombin. The crystal structures suggest a unique 2-step mechanism of thrombin recognition involving rapid electrostatics-driven association to form an initial glycosaminoglycan-bridged complex, followed by a large conformational rearrangement to form the productive Michaelis complex.


  • Organizational Affiliation

    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom. wl225@cam.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glia-derived nexin
A, B
379Homo sapiensMutation(s): 0 
Gene Names: SERPINE2PI7PN1
UniProt & NIH Common Fund Data Resources
Find proteins for P07093 (Homo sapiens)
Explore P07093 
Go to UniProtKB:  P07093
PHAROS:  P07093
GTEx:  ENSG00000135919 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07093
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid
C
2N/A
Glycosylation Resources
GlyTouCan:  G29057GU
GlyCosmos:  G29057GU
GlyGen:  G29057GU
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 140.65α = 90
b = 140.65β = 90
c = 93.55γ = 90
Software Package:
Software NamePurpose
DNAdata collection
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-08-15
    Type: Initial release
  • Version 1.1: 2015-04-22
    Changes: Non-polymer description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Source and taxonomy, Structure summary
  • Version 2.1: 2024-02-28
    Changes: Data collection, Database references, Structure summary
  • Version 2.2: 2024-03-13
    Changes: Source and taxonomy, Structure summary