1NEP

Crystal Structure Analysis of the Bovine NPC2 (Niemann-Pick C2) Protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure of a Cholesterol-binding Protein Deficient in Niemann-Pick Type C2 Disease

Friedland, N.Liou, H.-L.Lobel, P.Stock, A.M.

(2003) Proc Natl Acad Sci U S A 100: 2512-2517

  • DOI: https://doi.org/10.1073/pnas.0437840100
  • Primary Citation of Related Structures:  
    1NEP

  • PubMed Abstract: 

    Niemann-Pick disease type C2 (NP-C2) is a fatal hereditary disease characterized by accumulation of low-density lipoprotein-derived cholesterol in lysosomes. Here we report the 1.7-A resolution crystal structure of the cholesterol-binding protein deficient in this disease, NPC2, and the characterization of its ligand binding properties. Human NPC2 binds the cholesterol analog dehydroergosterol with submicromolar affinity at both acidic and neutral pH. NPC2 has an Ig-like fold stabilized by three disulfide bonds. The structure of the bovine protein reveals a loosely packed region penetrating from the surface into the hydrophobic core that forms adjacent small cavities with a total volume of approximately 160 A(3). We propose that this region represents the incipient cholesterol-binding site that dilates to accommodate an approximately 740-A(3) cholesterol molecule.


  • Organizational Affiliation

    Center for Advanced Biotechnology and Medicine, Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epididymal secretory protein E1130Bos taurusMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P79345 (Bos taurus)
Explore P79345 
Go to UniProtKB:  P79345
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP79345
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
B [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
C [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.157α = 90
b = 100.157β = 90
c = 100.157γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-01-28
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2011-11-16
    Changes: Atomic model
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary