4DTE

Crystal structure of zebrafish plasminogen activator inhibitor-1 (PAI-1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 

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Ligand Structure Quality Assessment 


This is version 1.7 of the entry. See complete history


Literature

Protein conformational change delayed by steric hindrance from an N-linked glycan.

Bager, R.Johansen, J.S.Jensen, J.K.Stensballe, A.Jendroszek, A.Buxbom, L.Sorensen, H.P.Andreasen, P.A.

(2013) J Mol Biol 425: 2867-2877

  • DOI: https://doi.org/10.1016/j.jmb.2013.05.007
  • Primary Citation of Related Structures:  
    4DTE, 4KDS

  • PubMed Abstract: 

    Very few studies have attributed a direct, active, functional role to N-linked glycans. We describe here an N-linked glycan with a unique role for maintaining the active conformation of a protein of the serpin family. The distinguishing feature of serpins is the "stressed-to-relaxed" transition, in which the reactive center loop inserts as a β-strand into the central β-sheet A. This transition forms the basis for the conversion of serpins to the inactive latent state. We demonstrate that plasminogen activator inhibitor-1 (PAI-1) from zebrafish converts to the latent state about 5-fold slower than human PAI-1. In contrast to human PAI-1, fish PAI-1 carries a single N-linked glycan at Asn185 in the gate region through which the reactive center loop passes during latency transition. While the latency transition of human PAI-1 is unaffected by deglycosylation, deglycosylated zebrafish PAI-1 (zfPAI-1) goes latent about 50-fold faster than the glycosylated zfPAI-1 and about 25-fold faster than non-glycosylated human PAI-1. X-ray crystal structure analysis of glycosylated fish PAI-1 confirmed the presence of an N-linked glycan in the gate region and a lack of glycan-induced structural changes. Thus, latency transition of zfPAI-1 is delayed by steric hindrance from the glycan in the gate region. Our findings reveal a previously unknown mechanism for inhibition of protein conformational changes by steric hindrance from N-linked glycans.


  • Organizational Affiliation

    Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus C, Denmark.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
A, B
374Danio rerioMutation(s): 0 
Gene Names: serpine1
UniProt
Find proteins for F1QRB8 (Danio rerio)
Explore F1QRB8 
Go to UniProtKB:  F1QRB8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupF1QRB8
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.16α = 90
b = 73.77β = 102.73
c = 91.75γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
xia2data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-27
    Type: Initial release
  • Version 1.1: 2013-04-10
    Changes: Other
  • Version 1.2: 2013-08-07
    Changes: Database references
  • Version 1.3: 2013-08-14
    Changes: Database references
  • Version 1.4: 2013-08-21
    Changes: Database references, Structure summary
  • Version 1.5: 2017-11-15
    Changes: Refinement description
  • Version 1.6: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.7: 2023-09-13
    Changes: Data collection, Database references, Refinement description, Structure summary