7Z7F

Crystal structure of YTHDF2 with compound YLI_DC1_005


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted IF3Click on this verticalbar to view details

This is version 1.2 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
IF3 (Subject of Investigation/LOI)
Query on IF3

Download Ideal Coordinates CCD File 
H [auth A]~{N}2,~{N}6,9-trimethylpurine-2,6-diamine
C8 H12 N6
YFZMXDSHFHHAQH-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
F [auth A]
G [auth A]
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

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

Download Ideal Coordinates CCD File 
E [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.23α = 90
b = 80.23β = 90
c = 114.01γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted IF3Click on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland310030B-189363

Revision History  (Full details and data files)

  • Version 1.0: 2022-03-23
    Type: Initial release
  • Version 1.1: 2022-09-28
    Changes: Database references
  • Version 1.2: 2024-01-31
    Changes: Data collection, Refinement description