4DRQ

Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52: Complex of FKBP51 with 2-(3-((R)-1-((S)-1-(3,5-dichlorophenylsulfonyl)piperidine-2-carbonyloxy)-3-(3,4-dimethoxy -phenyl)propyl)phenoxy)acetic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.151 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.138 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52.

Gopalakrishnan, R.Kozany, C.Wang, Y.Schneider, S.Hoogeland, B.Bracher, A.Hausch, F.

(2012) J Med Chem 55: 4123-4131

  • DOI: https://doi.org/10.1021/jm201747c
  • Primary Citation of Related Structures:  
    4DRQ

  • PubMed Abstract: 

    FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products, which tightly bind to most FKBP family members, including FKBP51 and FKBP52. A bioisosteric replacement of the α-ketoamide moiety of rapamycin and FK506 with a sulfonamide was envisaged with the retention of the conserved hydrogen bonds. A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular binding mode for one sulfonamide analogue was confirmed by X-ray crystallography.


  • Organizational Affiliation

    Max Planck Institute of Psychiatry, Kraepelinstrasse 2, 80804 Munich, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase FKBP5128Homo sapiensMutation(s): 0 
Gene Names: AIG6FKBP5FKBP51
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for Q13451 (Homo sapiens)
Explore Q13451 
Go to UniProtKB:  Q13451
PHAROS:  Q13451
GTEx:  ENSG00000096060 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13451
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0OS
Query on 0OS

Download Ideal Coordinates CCD File 
B [auth A]{3-[(1S)-1-[({(2S)-1-[(3,5-dichlorophenyl)sulfonyl]piperidin-2-yl}carbonyl)oxy]-3-(3,4-dimethoxyphenyl)propyl]phenoxy}acetic acid
C31 H33 Cl2 N O9 S
AOMAGJKZRYWVSR-SVBPBHIXSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0OS Binding MOAD:  4DRQ IC50: 2.26e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.151 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.138 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.966α = 90
b = 54.641β = 90
c = 56.596γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-18
    Type: Initial release
  • Version 1.1: 2012-05-23
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Advisory, Refinement description
  • Version 1.3: 2023-09-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description