PDBsum entry 6t0a

RNA binding protein

PDB id: 6t0a

Contents

Protein chains

164 a.a.

Ligands

M58 ×2

SO4 ×8

Waters ×325

PDB id:

6t0a

Name:

RNA binding protein

Title:

Crystal structure of ythdc1 with fragment 25 (psi_dc1_005)

Structure:

Ythdc1. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.02Å R-factor: 0.182 R-free: 0.229

Authors:

R.K.Bedi,D.Huang,P.Sledz,A.Caflisch

Key ref:

R.K.Bedi et al. (2020). Selectively Disrupting m⁶A-Dependent Protein-RNA Interactions with Fragments. ACS Chem Biol, 15, 618-625. PubMed id: 32101404 DOI: 10.1021/acschembio.9b00894

Date:

02-Oct-19 Release date: 04-Mar-20

Protein chains

Q96MU7  (YTDC1_HUMAN) -  YTH domain-containing protein 1 from Homo sapiens

Seq: 727 a.a.

Struc: 164 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/acschembio.9b00894

ACS Chem Biol 15:618-625 (2020)

PubMed id: 32101404

Selectively Disrupting m⁶A-Dependent Protein-RNA Interactions with Fragments.

R.K.Bedi, D.Huang, L.Wiedmer, Y.Li, A.Dolbois, J.A.Wojdyla, M.E.Sharpe, A.Caflisch, P.Sledz.

ABSTRACT

We report a crystallographic analysis of small-molecule ligands of the human YTHDC1 domain that recognizes N6-methylated adenine (m⁶A) in RNA. The 30 binders are fragments (molecular weight < 300 g mol^-1) that represent 10 different chemotypes identified by virtual screening. Despite the structural disorder of the binding site loop (residues 429-439), most of the 30 fragments emulate the two main interactions of the -NHCH₃ group of m⁶A. These interactions are the hydrogen bond to the backbone carbonyl of Ser378 and the van der Waals contacts with the tryptophan cage. Different chemical groups are involved in the conserved binding motifs. Some of the fragments show favorable ligand efficiency for YTHDC1 and selectivity against other m⁶A reader domains. The structural information is useful for the design of modulators of m⁶A recognition by YTHDC1.