4AW6

Crystal structure of the human nuclear membrane zinc metalloprotease ZMPSTE24 (FACE1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.246 
  • R-Value Observed: 0.247 

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This is version 1.4 of the entry. See complete history


Literature

The Structural Basis of Zmpste24-Dependent Laminopathies.

Quigley, A.Dong, Y.Y.Pike, A.C.W.Dong, L.Shrestha, L.Berridge, G.Stansfeld, P.J.Sansom, M.S.P.Edwards, A.M.Bountra, C.von Delft, F.Bullock, A.N.Burgess-Brown, N.A.Carpenter, E.P.

(2013) Science 339: 1604

  • DOI: https://doi.org/10.1126/science.1231513
  • Primary Citation of Related Structures:  
    2YPT, 4AW6

  • PubMed Abstract: 

    Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane α-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Oxford, Oxford, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CAAX PRENYL PROTEASE 1 HOMOLOGA,
B,
C [auth D],
D [auth E]
482Homo sapiensMutation(s): 1 
EC: 3.4.24.84
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for O75844 (Homo sapiens)
Explore O75844 
Go to UniProtKB:  O75844
PHAROS:  O75844
GTEx:  ENSG00000084073 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75844
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.246 
  • R-Value Observed: 0.247 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.987α = 76.73
b = 95.451β = 79.64
c = 131.095γ = 72.61
Software Package:
Software NamePurpose
XDSdata reduction
Aimlessdata scaling
SHELXDphasing
SOLVEphasing
BUSTER-TNTrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-25
    Type: Initial release
  • Version 1.1: 2012-12-05
    Changes: Database references, Structure summary
  • Version 1.2: 2013-05-15
    Changes: Database references
  • Version 1.3: 2018-01-24
    Changes: Database references
  • Version 1.4: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other