2P4E

Crystal Structure of PCSK9


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.

Cunningham, D.Danley, D.E.Geoghegan, K.F.Griffor, M.C.Hawkins, J.L.Subashi, T.A.Varghese, A.H.Ammirati, M.J.Culp, J.S.Hoth, L.R.Mansour, M.N.McGrath, K.M.Seddon, A.P.Shenolikar, S.Stutzman-Engwall, K.J.Warren, L.C.Xia, D.Qiu, X.

(2007) Nat Struct Mol Biol 14: 413-419

  • DOI: https://doi.org/10.1038/nsmb1235
  • Primary Citation of Related Structures:  
    2P4E

  • PubMed Abstract: 

    Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism. The structure of human PCSK9 shows the subtilisin-like catalytic site blocked by the prodomain in a noncovalent complex and inaccessible to exogenous ligands, and that the C-terminal domain has a novel fold. Biosensor studies show that PCSK9 binds the extracellular domain of LDL receptor with K(d) = 170 nM at the neutral pH of plasma, but with a K(d) as low as 1 nM at the acidic pH of endosomes. The D374Y gain-of-function mutant, associated with hypercholesterolemia and early-onset cardiovascular disease, binds the receptor 25 times more tightly than wild-type PCSK9 at neutral pH and remains exclusively in a high-affinity complex at the acidic pH. PCSK9 may diminish LDL receptors by a mechanism that requires direct binding but not necessarily receptor proteolysis.


  • Organizational Affiliation

    Pfizer Inc., Eastern Point Road, Groton, Connecticut 06430, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proprotein convertase subtilisin/kexin type 9A [auth P],
B [auth A]
692Homo sapiensMutation(s): 0 
Gene Names: PCSK9NARC1
EC: 3.4.21
UniProt & NIH Common Fund Data Resources
Find proteins for Q8NBP7 (Homo sapiens)
Explore Q8NBP7 
Go to UniProtKB:  Q8NBP7
PHAROS:  Q8NBP7
GTEx:  ENSG00000169174 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8NBP7
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.81α = 90
b = 70.67β = 90
c = 150.02γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-04-10
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description