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7YYF

Orthorombic crystal structure of YTHDF1 YTH domain (G459N mutant) form II

Summary for 7YYF
Entry DOI10.2210/pdb7yyf/pdb
Related7YYE
DescriptorYTH domain-containing family protein 1 (2 entities in total)
Functional Keywordsmrna binding and stability, rna binding protein
Biological sourceHomo sapiens (human)
Total number of polymer chains4
Total formula weight93292.88
Authors
Dalle Vedove, A.,Cazzanelli, G.,Lolli, G. (deposition date: 2022-02-17, release date: 2023-03-01, Last modification date: 2024-03-13)
Primary citationCazzanelli, G.,Dalle Vedove, A.,Spagnolli, G.,Terruzzi, L.,Colasurdo, E.,Boldrini, A.,Patsilinakos, A.,Sturlese, M.,Grottesi, A.,Biasini, E.,Provenzani, A.,Quattrone, A.,Lolli, G.
Pliability in the m 6 A-Binding Region Extends Druggability of YTH Domains.
J.Chem.Inf.Model., 2024
Cited by
PubMed Abstract: Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing the mA mark on mRNA and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present in the organization of the mA-binding pocket. Here, we present new crystallographic structures of the YTH domain of YTHDF1, accompanied by computational studies, showing that this domain can exist in different stable conformations separated by a significant energetic barrier. During the transition, additional conformations are explored, with peculiar druggable pockets appearing and offering new opportunities for the design of YTH-interfering small molecules.
PubMed: 38417111
DOI: 10.1021/acs.jcim.4c00051
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.3 Å)
Structure validation

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