7YXE

Crystal structure of YTHDF2 with compound ZA_143


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.211 

Starting Model: experimental
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This is version 1.3 of the entry. See complete history


Literature

Fragment Ligands of the m 6 A-RNA Reader YTHDF2.

Nai, F.Nachawati, R.Zalesak, F.Wang, X.Li, Y.Caflisch, A.

(2022) ACS Med Chem Lett 13: 1500-1509

  • DOI: https://doi.org/10.1021/acsmedchemlett.2c00303
  • Primary Citation of Related Structures:  
    7R5F, 7R5L, 7R5W, 7YWB, 7YX6, 7YXE, 7Z26, 7Z4U, 7Z54, 7Z5M, 7Z7B, 7Z7F, 7Z8P, 7Z8W, 7Z8X, 7Z92, 7Z93, 7ZG4

  • PubMed Abstract: 

    We report 17 small-molecule ligands that compete with N6 -methyladenosine (m 6 A) for binding to the m 6 A-reader domain of YTHDF2 (YT521-B homology domain family 2). We determined their binding mode at high resolution by X-ray crystallography and quantified their affinity by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative have favorable ligand efficiencies of 0.47 and 0.38 kcal mol -1 per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.


  • Organizational Affiliation

    Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
YTH domain-containing family protein 2
A, B
167Homo sapiensMutation(s): 0 
Gene Names: YTHDF2HGRG8
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y5A9 (Homo sapiens)
Explore Q9Y5A9 
Go to UniProtKB:  Q9Y5A9
PHAROS:  Q9Y5A9
GTEx:  ENSG00000198492 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y5A9
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I82 (Subject of Investigation/LOI)
Query on I82

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
~{N}-methyl-3-phenyl-2~{H}-pyrazolo[4,3-d]pyrimidin-7-amine
C12 H11 N5
XIEMFNUUOUPBSW-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
H [auth B],
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth B]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
J [auth B]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
I82 BindingDB:  7YXE IC50: 1.61e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.211 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.16α = 90
b = 80.16β = 90
c = 114.04γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland310030B-189363

Revision History  (Full details and data files)

  • Version 1.0: 2022-03-02
    Type: Initial release
  • Version 1.1: 2022-07-06
    Changes: Derived calculations
  • Version 1.2: 2022-09-28
    Changes: Database references
  • Version 1.3: 2024-01-31
    Changes: Data collection, Refinement description