caa a22 4500 605513171 CHVBK 20210128100659.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00894-015-2655-8 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2655-8 Curcumin and hydroxamate-derivative (PCI-34058) interfere with histone deacetylase I catalytic core Asp-His charge relay system: atomistic simulation studies [Elektronische Daten] [I. Omotuyi, M. Abiodun, K. Komolafe, O. Ejelonu, O. Olusanya] Histone deacetylases (HDACs) are representative targets for the natural and synthetic chemicals used to transform cells to confer antitumor properties. In the current study, curcumin and hydroxamate-derivative PCI-34058-bound HDAC1 were subjected to atomistic simulation. The results support the view that fitting of curcumin and PCI-34058 within the HDAC1 pocket depends on extensive interactions between the aromatic moieties of the inhibitors and the extensive network of aromatic amino acid side chains lining the pocket of HDAC1. The interaction forces a local perturbation of the coiled structures connecting the pocket residues resulting in ligand-induced tightening of the pocket. In addition to the competitive occupancy of the histone-acetyl-lysine binding pocket by the inhibitors, interference with the in-pocket aspartate-histidine (ASP-HIS) charge relay system was also observed in inhibitor-bound HDAC1 systems. In conclusion, curcumin and PCI-34058-mediated ligand-dependent HDAC1 tunnel closure interferes negatively with the ASP-HIS charge relay system in HDAC1. Future design of HDAC inhibitors may benefit from optimizing competitive interaction with the ligand site and interference with the charge relay system. Springer-Verlag Berlin Heidelberg, 2015 HDAC1 nationallicence Curcumin nationallicence Hydroxamate-derivative nationallicence Charge-relay system nationallicence Omotuyi I. Department of Pharmacology and Therapeutic Innovation, Nagasaki University, 1-14 Bunkyo-machi, 852-8531, Nagasaki, Japan aut Abiodun M. Department of Bioresource and Biotechnology, Kyushu University, 6-10-1 Hakozaki, 8120-8581, Higashi, Fukuoka, Japan aut Komolafe K. Department of Biochemistry, Federal University Oye-Ekiti, Oye, Ekiti, Nigeria aut Ejelonu O. Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria aut Olusanya O. Department of Biochemistry, Faculty of Life Sciences, University of Benin, PMB 1154, Benin City, Edo, Nigeria aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/5(2015-05-01), 1-8 1610-2940 21:5<1 2015 21 894 https://doi.org/10.1007/s00894-015-2655-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2655-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Omotuyi I. Department of Pharmacology and Therapeutic Innovation, Nagasaki University, 1-14 Bunkyo-machi, 852-8531, Nagasaki, Japan aut NATIONALLICENCE 700 1- Abiodun M. Department of Bioresource and Biotechnology, Kyushu University, 6-10-1 Hakozaki, 8120-8581, Higashi, Fukuoka, Japan aut NATIONALLICENCE 700 1- Komolafe K. Department of Biochemistry, Federal University Oye-Ekiti, Oye, Ekiti, Nigeria aut NATIONALLICENCE 700 1- Ejelonu O. Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria aut NATIONALLICENCE 700 1- Olusanya O. Department of Biochemistry, Faculty of Life Sciences, University of Benin, PMB 1154, Benin City, Edo, Nigeria aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/5(2015-05-01), 1-8 1610-2940 21:5<1 2015 21 894