Abstract
Cytochrome P450 14α-sterol demethylase (CYP51), the key enzyme in sterol biosynthesis pathway, is an important target protein of cholesterol-lowering agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51 family members. In the present study, we have chosen four representative inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb), and voriconazole (Vor), and launched to investigate the binding features of CYP51B-inhibitor and gating characteristics via molecular docking and molecular dynamics (MD) simulations. The results show that the ranking of binding affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the strongest binding affinity, whereas Flu shows the weakest binding affinity. More importantly, based on the calculated binding free energy results, we hypothesize that the nonpolar interactions are the most important contributors, and three key residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor binding. Besides, residue Phe180 may play a molecular switch role in the process of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results show that the major tunnel of Din, Flu, and Teb is located between helix K, FG loop,...Continue Reading
References
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A BellamineM R Waterman
Jul 13, 2000·Biochemical and Biophysical Research Communications·Y YoshidaO Gotoh
Jun 28, 2001·Journal of Clinical Microbiology·E MelladoJ L Rodriguez-Tudela
Jan 30, 2002·Trends in Molecular Medicine·Antonella LupettiSteven Kelly
Feb 7, 2003·Journal of Medicinal Chemistry·Haitao JiJü Zhu
Feb 21, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Leonard B Johnson, Carol A Kauffman
Mar 18, 2004·Molecular and Cellular Endocrinology·Galina I Lepesheva, Michael R Waterman
Mar 17, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Yuri Aoyama
Sep 13, 2005·Biochemical and Biophysical Research Communications·Michael R Waterman, Galina I Lepesheva
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Jun 24, 2006·BMC Bioinformatics·Martin PetrekJirí Damborský
Jul 18, 2006·Nucleic Acids Research·Joe DundasJie Liang
Sep 12, 2006·Biochimica Et Biophysica Acta·Galina I Lepesheva, Michael R Waterman
May 15, 2007·Chemotherapy·A I AllerE Martín-Mazuelos
Nov 16, 2007·Proteins·Weihua LiHualiang Jiang
Mar 28, 2008·Seminars in Respiratory and Critical Care Medicine·Dimitrios I Zonios, John E Bennett
Nov 22, 2008·Molecular & Cellular Proteomics : MCP·Tingjun HouWei Wang
May 15, 2009·The Journal of Physical Chemistry. B·Kakali Sen, John C Hackett
Oct 14, 2010·Archives of Biochemistry and Biophysics·Kip P ConnerWilliam M Atkins
Nov 25, 2011·The FEBS Journal·Gregor LorbekDamjana Rozman
Nov 28, 2012·Chemistry : a European Journal·Ying-Lu CuiChia-Chung Sun
May 25, 2013·Journal of Chemical Information and Modeling·Jonathan D TyzackRobert C Glen
Nov 12, 2013·Journal of Chemical Information and Modeling·Ying-Lu CuiHong-Xing Zhang
Jun 13, 2015·Journal of Biomolecular Structure & Dynamics·Jing-Rong FanHong-Xing Zhang
Aug 14, 2015·The Journal of Biological Chemistry·Tatiana Y HargroveGalina I Lepesheva
Citations
Mar 10, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Omar Gómez-GarcíaCecilio Álvarez-Toledano
Jan 19, 2019·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Mahdi AbastabarMohammad T Hedayati
May 8, 2019·Journal of Biomolecular Structure & Dynamics·Tayane Honorato Siqueira, Leandro Martínez
Jan 4, 2021·Environmental Pollution·Ana Lopez-AntiaRafael Mateo