3SQO

PCSK9 J16 Fab complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates.

Liang, H.Chaparro-Riggers, J.Strop, P.Geng, T.Sutton, J.E.Tsai, D.Bai, L.Abdiche, Y.Dilley, J.Yu, J.Wu, S.Chin, S.M.Lee, N.A.Rossi, A.Lin, J.C.Rajpal, A.Pons, J.Shelton, D.L.

(2012) J Pharmacol Exp Ther 340: 228-236

  • DOI: https://doi.org/10.1124/jpet.111.187419
  • Primary Citation of Related Structures:  
    3SQO

  • PubMed Abstract: 

    Proprotein convertase substilisin/kexin type 9 (PCSK9) promotes the degradation of low-density lipoprotein (LDL) receptor (LDLR) and thereby increases serum LDL-cholesterol (LDL-C). We have developed a humanized monoclonal antibody that recognizes the LDLR binding domain of PCSK9. This antibody, J16, and its precursor mouse antibody, J10, potently inhibit PCSK9 binding to the LDLR extracellular domain and PCSK9-mediated down-regulation of LDLR in vitro. In vivo, J10 effectively reduces serum cholesterol in C57BL/6 mice fed normal chow. J16 reduces LDL-C in healthy and diet-induced hypercholesterolemic cynomologous monkeys, but does not significantly affect high-density lipoprotein-cholesterol. Furthermore, J16 greatly lowered LDL-C in hypercholesterolemic monkeys treated with the HMG-CoA reductase inhibitor simvastatin. Our data demonstrate that anti-PCSK9 antibody is a promising LDL-C-lowering agent that is both efficacious and potentially additive to current therapies.


  • Organizational Affiliation

    Rinat Laboratories, Pfizer Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA. hong.liang@pfizer.com


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proprotein convertase subtilisin/kexin type 9540Homo sapiensMutation(s): 0 
Gene Names: PCSK9NARC1PSEC0052
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
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
J16 Heavy chainB [auth H]219Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
J16 Light chainC [auth L]214Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
PCSK9 prodomainD [auth P]122Homo sapiensMutation(s): 0 
Gene Names: PCSK9NARC1PSEC0052
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.921α = 90
b = 70.981β = 95.9
c = 109.156γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection

Structure Validation

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Entry History 

Deposition Data

  • Released Date: 2012-05-16 
  • Deposition Author(s): Strop, P.

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-16
    Type: Initial release