1TYR

TRANSTHYRETIN COMPLEX WITH RETINOIC ACID


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the transthyretin--retinoic-acid complex

Zanotti, G.D'Acunto, M.R.Malpeli, G.Folli, C.Berni, R.

(1995) Eur J Biochem 234: 563-569

  • DOI: https://doi.org/10.1111/j.1432-1033.1995.563_b.x
  • Primary Citation of Related Structures:  
    1TYR

  • PubMed Abstract: 

    Retinoids are quite insoluble and chemically unstable compounds in the aqueous medium, such that natural retinoids need to be bound to specific retinoid-binding proteins to be protected, solubilized and transported in body fluids. All-trans retinoic acid exhibits a relatively high affinity for thyroxine-binding transthyretin in vitro and this protein is a good candidate for the transport of retinoic acid administered as pharmacological or antitumor agent. To define structural features essential for the recognition by transthyretin of a ligand which is structurally unrelated to thyroxine, we have cocrystallized human transthyretin with retinoic acid and determined its structure at 0.18-nm resolution. The retinoid fits into the two chemically identical thyroxine-binding sites, which are located in the central channel that runs through the tetrameric transthyretin. The cyclohexene ring of the bound retinoid is innermost, occupying the same position of the phenolic ring of the bound 3,3'-diiodo-L-thyronine, whereas the carboxylate group, like the same group of the thyroid hormone, participates in an ionic interaction with the Lys15 side chain at the entrance of the channel. Despite the fact that transthyretin was cocrystallized with all-trans-retinoic acid, the isoprene chain of the bound retinoid has been found in a non-extended conformation. This feature, that allows the carboxylate to orient in a manner suitable for ion-pair association with the Lys15 side chain, is attributable to the conversion of all-trans-retinoic acid into cis-isomers or folded conformers. It is concluded that the presence, in an essentially hydrophobic molecular core of the appropriate size, of a negatively charged group at the correct position is a crucial requirement for ligand-transthyretin recognition. Whereas the binding of the ligand has no remarkable consequences for the protein structure, all-trans-retinoic acid undergoes structural changes such as to interact favorably with residues present in the thyroxine-binding sites, resembling roughly the natural ligand.


  • Organizational Affiliation

    Department of Organic Chemistry, University of Padova, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRANSTHYRETIN
A, B
127Homo sapiensMutation(s): 0 
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
9CR
Query on 9CR

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(9cis)-retinoic acid
C20 H28 O2
SHGAZHPCJJPHSC-ZVCIMWCZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
9CR Binding MOAD:  1TYR Kd: 100 (nM) from 1 assay(s)
REA PDBBind:  1TYR Kd: 100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.8α = 90
b = 86.22β = 90
c = 65.78γ = 90
Software Package:
Software NamePurpose
TNTrefinement
SAINTdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-09-15
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2016-11-09
    Changes: Non-polymer description
  • Version 1.4: 2017-11-29
    Changes: Derived calculations, Other