Conformational dynamics underlies different functions of human KDM7 histone demethylases
Document Type
Article
Publication Date
2-28-2019
Abstract
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.
Publication Title
Chemistry - A European Journal
Recommended Citation
Chaturvedi, S.,
Ramanan, R.,
&
Waheed, S.
(2019).
Conformational dynamics underlies different functions of human KDM7 histone demethylases.
Chemistry - A European Journal.
http://doi.org/10.1002/chem.201900492
Retrieved from: https://digitalcommons.mtu.edu/chemistry-fp/125
Publisher's Statement
© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. Publisher's version of record: https://doi.org/10.1002/chem.201900492