Abstract
Mutations of CYP51A protein (Cytochrome P450 14-α Sterol demethylase) play a central role in the azole resistance of Aspergillus fumigatus. The available structural models of CYP51A protein of A. fumigatus are built based on that of Homo sapiens and that of Mycobacterium tuberculosis, of which the amino acid homology is only 38% and 29% compared with CYP51A protein of A. fumigatus, respectively. In the present study, we constructed a new 3D structural model of A. fumigatus CYP51A protein based on a recently resolved crystal structure of the homologous protein in the fungus S. cerevisiae, which shares 50% amino acid homology with A. fumigatus CYP51A protein. Three azole molecules, itraconazole, voriconazole, and posaconazole, were docked to the wild-type and the mutant A. fumigatus CYP51A protein models, respectively, to illustrate the impact of cyp51A mutations to azole-resistance. We found the mutations that occurred at L98, M220, and Y431 positions would decrease the binding affinity of azoles to the CYP51A protein and therefore would reduce their inhibitory effects. Additionally, the mutations of L98 and G432 would reduce the stability of the protein, which might lead to conformational change of its binding pocket and eventu...Continue Reading
References
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Jan 1, 1997·Methods in Enzymology·D EisenbergJ U Bowie
Aug 13, 1999·Journal of Enzyme Inhibition·D F LewisM H Tarbit
Jan 18, 2002·Antimicrobial Agents and Chemotherapy·J Mosquera, D W Denning
Jul 24, 2002·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
Aug 9, 2002·The New England Journal of Medicine·Raoul HerbrechtUNKNOWN Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillu
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·T M Diaz-GuerraJ L Rodriguez-Tudela
Jan 27, 2004·Antimicrobial Agents and Chemotherapy·Li XiaoPaul M McNicholas
Jun 25, 2004·Antimicrobial Agents and Chemotherapy·E MelladoJ L Rodriguez-Tudela
Jan 22, 2005·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
Dec 27, 2005·Current Drug Targets·Axel A Brakhage
Jun 16, 2006·BMC Bioinformatics·Scott MontgomerieDavid S Wishart
Oct 13, 2006·International Journal of Antimicrobial Agents·Susan J HowardDavid W Denning
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Mar 21, 2007·Antimicrobial Agents and Chemotherapy·E MelladoJ L Rodríguez-Tudela
Nov 8, 2007·FEMS Microbiology Letters·Li ZhaoWenjing Xiao
Apr 29, 2008·Protein Science : a Publication of the Protein Society·Per LarssonArne Elofsson
Sep 5, 2008·Lipids·Galina I LepeshevaMichael R Waterman
Nov 13, 2008·PLoS Medicine·Eveline SneldersPaul E Verweij
May 28, 2009·Antimicrobial Agents and Chemotherapy·Chunquan ShengWannian Zhang
Jun 2, 2009·Current Opinion in Structural Biology·Hitomi Hasegawa, Liisa Holm
Apr 14, 2010·Antimicrobial Agents and Chemotherapy·Eveline SneldersWillem J G Melchers
Oct 7, 2010·Journal of Molecular Modeling·Pandian SokkarMurugesan Ramachandran
Feb 9, 2011·Antimicrobial Agents and Chemotherapy·M G FraczekP Bowyer
Aug 24, 2011·Retrovirology·Jessica Radzio, Nicolas Sluis-Cremer
Oct 27, 2011·The Journal of Antimicrobial Chemotherapy·Anuradha ChowdharyJacques F Meis
Jan 19, 2013·Molecular Biology and Evolution·Kazutaka Katoh, Daron M Standley
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Brian C MonkRobert M Stroud
Apr 22, 2015·Antimicrobial Agents and Chemotherapy·Musang LiuWeida Liu
Citations
Sep 7, 2016·Frontiers in Microbiology·Wesley J MairFrancisco J Lopez-Ruiz
Sep 2, 2016·Medical Mycology Journal·Masato Tashiro, Koichi Izumikawa
Feb 22, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Masaki IkedaHitoshi Ashida
Oct 11, 2017·Medical Mycology·Anthony Nash, Johanna Rhodes
Mar 8, 2017·Antimicrobial Agents and Chemotherapy·Sanjoy PaulW Scott Moye-Rowley
Jul 7, 2016·Antimicrobial Agents and Chemotherapy·Florencia LeonardelliGuillermo Garcia-Effron
Sep 15, 2017·Clinical Microbiology Reviews·Anna DudakovaOliver Bader
May 31, 2018·Angewandte Chemie·Stefano AgnelloRainer Riedl
May 8, 2019·Antimicrobial Agents and Chemotherapy·Alba Pérez-CanteroJavier Capilla
Sep 20, 2017·Antimicrobial Agents and Chemotherapy·J B BuilP E Verweij
Aug 28, 2019·Antimicrobial Agents and Chemotherapy·Jessica J TalbotJos Houbraken
Mar 14, 2019·MBio·Sanjoy PaulW Scott Moye-Rowley
Feb 11, 2020·Frontiers in Microbiology·Peiying ChenLing Lu
Mar 15, 2020·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Natália Sayuri WassanoAndré Damasio
Nov 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eftichia KritsiPanagiotis Zoumpoulakis
Jun 28, 2017·Mycopathologia·A HamprechtE Dannaoui
Jul 13, 2017·Marine Drugs·Lan-Ting XinChang-Yun Wang
Nov 26, 2020·MBio·Amelia E BarberOliver Kurzai
Dec 2, 2020·Journal of Fungi·Irene Gonzalez-JimenezEmilia Mellado
Jan 2, 2021·Frontiers in Microbiology·Bart FraaijeJohn Lucas
Jul 22, 2019·Fungal Genetics and Biology : FG & B·Margriet W J HokkenP E Verweij
Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Mark T RoundtreeWilliam J Steinbach
Sep 11, 2018·Metabolic Engineering Communications·Jong-Won LeeCong T Trinh
May 27, 2021·Studies in Mycology·A ArastehfarM Hoenigl
Jul 3, 2021·Pathogens·Yuying FanJianping Xu
May 7, 2021·Mycopathologia·Musang LiuWeida Liu
Sep 25, 2021·Mycoses·Hidetaka MajimaKatsuhiko Kamei
Nov 13, 2021·Mycoses·Anke BurmesterCornelia Wiegand