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cc-by (c) Pieters, Bas J. G. E. et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/196125

Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger

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The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the positively charged trimethyllysine by the electron-rich aromatic cage containing PHD3 finger of KDM5A. The aromatic character of two tryptophan residues that solely constitute the aromatic cage of KDM5A was fine-tuned by the incorporation of fluorine substituents. Our thermodynamic analyses reveal that the wild-type and fluorinated KDM5A PHD3 fingers associate equally well with trimethyllysine. This work demonstrates that the biomolecular recognition of trimethyllysine by fluorinated aromatic cages is associated with weaker cation-π interactions that are compensated by the energetically more favourable trimethyllysine-mediated release of high-energy water molecules that occupy the aromatic cage.

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PIETERS, Bas j. g. e., WUTS, Maud h. m., POATER I TEIXIDOR, Jordi, KUMAR, Kiran, WHITE, Paul b., KAMPS, Jos j. a. g., SHERMAN, Woody, PRUIJN, Ger j. m., PATON, Robert s., BEUMIMG, Thijs, BICKELHAUPT, F. matthias, MECINOVIĆ, Jasmin. Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger. _Communications Chemistry_. 2020. Vol. 3, núm. 69. [consulta: 24 de gener de 2026]. ISSN: 2399-3669. [Disponible a: https://hdl.handle.net/2445/196125]

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