Conformational Dynamics Underlies Different Functions of Human KDM7 Histone Demethylases

Shobhit Chaturvedi, Rajeev Ramanan, Sodiq O. Waheed, Jon Ainsley, Martin Evison, Jenny Ames, Christopher J. Schofield, Tatyana Karabencheva-Christova, Christo Christov

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
27 Downloads (Pure)


The human KDM7 subfamily histone H3 Nɛ‐methyl lysine demethylases PHF8 (KDM7B) and KIAA1718 (KDM7A) have different substrate selectivities and are linked to genetic diseases and cancer. We describe experimentally based computational studies revealing that flexibility of the region linking the PHD finger and JmjC domains in PHF8 and KIAA1718 regulates inter‐domain interactions, the nature of correlated motions, and ultimately H3 binding and demethylation site selectivity. F279S an X‐linked mental retardation mutation in PHF8 is involved in correlated motions with the iron ligands and second sphere residues. The calculations reveal key roles of a flexible protein environment in productive formation of enzyme‐substrate complexes and suggest targeting the flexible KDM7 linker region is of interest from a medicinal chemistry perspective.
Original languageEnglish
Pages (from-to)5422-5426
Number of pages5
JournalChemistry - A European Journal
Issue number21
Early online date26 Mar 2019
Publication statusPublished - 11 Apr 2019


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