Yudibeth Sixto-Lopez is a Ph.D. student from Escuela Superior de Medicina of the Instituto Politecnico Nacional, Mexico where she also did her Master. She performed an academic stay at University of Granada, Spain. She has published 6 papers in reputed journals.
Abstract
Histone deacetylases (HDACs) are a family of proteins whose main function is the removal of acetyl groups from lysine residues located on histone and non-histone substrates, which regulates gene transcription and other activities in cells. HDACs are composed of 18 isoforms grouped into four classes, three classes are zinc-dependent, class I (HDAC1, 2, 3 and 8), II (HDAC4, 5, 6, 7, 9 and 1) and IV (HDAC11); and the other is NAD+-dependent (class III), so-called “sirtuins”1. HDAC1 has been involved in cancer development, thus its inhibition has emerged as a promissory therapeutic strategy, and the acquisition of the structural knowledge could help in the rational drug design in order to achieve selective inhibitors2. HDAC1, possess two additional conserved metal binding sites (Site 1 and Site 2), also described in other isoforms, suggesting a possible structural role that affects HDAC catalytical activity. In this work, we performed molecular dynamics (MD) simulation of HDAC1 in order to reveal structural details about these sites and how it affects the interactions with reported HDAC inhibitors. Our results suggest that these sites play an important structural role, since it impacts in the structural flexibility of HDCA1 reflected in parameters like RMSD and RMSF, it also affects the molecular recognition between the inhibitor and HDAC1.
