2G5U

Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity

Purkey, H.E.Palaninathan, S.K.Kent, K.C.Smith, C.Safe, S.H.Sacchettini, J.C.Kelly, J.W.

(2004) Chem Biol 11: 1719-1728

  • DOI: https://doi.org/10.1016/j.chembiol.2004.10.009
  • Primary Citation of Related Structures:  
    2G5U, 2G9K, 2GAB

  • PubMed Abstract: 

    Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) are known to bind to transthyretin (TTR) in vitro, possibly explaining their bioaccumulation, rodent toxicity, and presumed human toxicity. Herein, we show that several OH-PCBs bind selectively to TTR in blood plasma; however, only one of the PCBs tested binds TTR in plasma. Some of the OH-PCBs displace thyroid hormone (T4) from TTR, rationalizing the toxicity observed in rodents, where TTR is the major T4 transporter. Thyroid binding globulin and albumin are the major T4 carriers in humans, making it unlikely that enough T4 could be displaced from TTR to be toxic. OH-PCBs are excellent TTR amyloidogenesis inhibitors in vitro because they bind to the TTR tetramer, imparting kinetic stability under amyloidogenic denaturing conditions. Four OH-PCB/TTR cocrystal structures provide further insight into inhibitor binding interactions.


  • Organizational Affiliation

    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transthyretin
A, B
127Homo sapiensMutation(s): 0 
Gene Names: TTRPALB
UniProt & NIH Common Fund Data Resources
Find proteins for P02766 (Homo sapiens)
Explore P02766 
Go to UniProtKB:  P02766
PHAROS:  P02766
GTEx:  ENSG00000118271 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02766
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PCQ
Query on PCQ

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
3,5,3',5'-TETRACHLORO-BIPHENYL-4,4'-DIOL
C12 H6 Cl4 O2
YCYDXOVJXVALHY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PCQ Binding MOAD:  2G5U Kd: 3.2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.239α = 90
b = 85.841β = 90
c = 64.793γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
AMoREphasing
REFMACrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-03-07
    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