1FKN

Structure of Beta-Secretase Complexed with Inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.

Hong, L.Koelsch, G.Lin, X.Wu, S.Terzyan, S.Ghosh, A.K.Zhang, X.C.Tang, J.

(2000) Science 290: 150-153

  • DOI: https://doi.org/10.1126/science.290.5489.150
  • Primary Citation of Related Structures:  
    1FKN

  • PubMed Abstract: 

    Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.


  • Organizational Affiliation

    Protein Studies Program and Crystallography Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MEMAPSIN 2
A, B
391Homo sapiensMutation(s): 0 
EC: 3.4.23.46
UniProt & NIH Common Fund Data Resources
Find proteins for P56817 (Homo sapiens)
Explore P56817 
Go to UniProtKB:  P56817
PHAROS:  P56817
GTEx:  ENSG00000186318 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56817
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
inhibitor
C, D
7N/AMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.652α = 90
b = 85.853β = 101.36
c = 109.237γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-10-09
    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
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations