7Z7B

Crystal structure of YTHDF2 with compound YLI_DC1_003

PDB DOI: https://doi.org/10.2210/pdb7Z7B/pdb

Classification: RNA BINDING PROTEIN
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2022-03-15 Released: 2022-06-22
Deposition Author(s): Nai, F., Li, Y., Dolbois, A., Caflisch, A.
Funding Organization(s): Swiss National Science Foundation

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.193
R-Value Work: 0.178
R-Value Observed: 0.209

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

PubMed: 36110386 Search on PubMedSearch on PubMed Central
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 ⁶A) for binding to the m ⁶A-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.

Macromolecule Content

Total Structure Weight: 39.87 kDa
Atom Count: 2,624
Modelled Residue Count: 297
Deposited Residue Count: 334
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
YTH domain-containing family protein 2	A, B	167	Homo sapiens	Mutation(s): 0 Gene Names: YTHDF2, HGRG8
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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9Y5A9
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
OYK (Subject of Investigation/LOI) Query on OYK Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain M [auth B] MOL2 format, chain I [auth A] MOL2 format, chain M [auth B] mmCIF format, chain I [auth A] mmCIF format, chain M [auth B]	I [auth A], M [auth B]	~{N},9-dimethylpurin-6-amine C₇ H₉ N₅ GRDLXXJSRHDATN-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain M [auth B] Interactions & Density Focus chain I [auth A] Focus chain M [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain J [auth A] SDF format, chain L [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain J [auth A] MOL2 format, chain L [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain J [auth A] mmCIF format, chain L [auth B]	C [auth A] D [auth A] E [auth A] F [auth A] J [auth A] C [auth A], D [auth A], E [auth A], F [auth A], J [auth A], L [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth A] Focus chain L [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth A] Focus chain L [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain N [auth B] MOL2 format, chain N [auth B] mmCIF format, chain N [auth B]	N [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain N [auth B] Interactions & Density Focus chain N [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain K [auth A] SDF format, chain O [auth B] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain K [auth A] MOL2 format, chain O [auth B] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain K [auth A] mmCIF format, chain O [auth B]	G [auth A], H [auth A], K [auth A], O [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain K [auth A] Focus chain O [auth B] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain K [auth A] Focus chain O [auth B]