3QNF

Crystal structure of the open state of human endoplasmic reticulum aminopeptidase 1 ERAP1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming.

Kochan, G.Krojer, T.Harvey, D.Fischer, R.Chen, L.Vollmar, M.von Delft, F.Kavanagh, K.L.Brown, M.A.Bowness, P.Wordsworth, P.Kessler, B.M.Oppermann, U.

(2011) Proc Natl Acad Sci U S A 108: 7745-7750

  • DOI: https://doi.org/10.1073/pnas.1101262108
  • Primary Citation of Related Structures:  
    2YD0, 3QNF

  • PubMed Abstract: 

    Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)(18)-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K(528)R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endoplasmic reticulum aminopeptidase 1
A, B, C
954Homo sapiensMutation(s): 0 
Gene Names: ERAP1APPILSARTS1KIAA0525UNQ584/PRO1154
EC: 3.4.11
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZ08 (Homo sapiens)
Explore Q9NZ08 
Go to UniProtKB:  Q9NZ08
PHAROS:  Q9NZ08
GTEx:  ENSG00000164307 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZ08
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G04854NQ
GlyCosmos:  G04854NQ
GlyGen:  G04854NQ
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.246α = 90
b = 132.816β = 90
c = 233.687γ = 90
Software Package:
Software NamePurpose
GDAdata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-01-31
    Changes: Structure summary
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-09-13
    Changes: Data collection, Database references, Refinement description, Structure summary