Imperial College London
Portrait Picture

DrJohannaRhodes

Faculty of Medicine, School of Public Health

Honorary Research Fellow
 
 
 
//

Contact

 

johanna.rhodes

 
 
//

Location

 

Desk 17Sir Michael Uren HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@unpublished{Nash:2016:10.1101/088468,
author = {Nash, A and Rhodes, J},
doi = {10.1101/088468},
title = {Simulations of<i>CYP51A</i>from<i>Aspergillus fumigatus</i>in a model bilayer provide insights into triazole drug resistance},
url = {http://dx.doi.org/10.1101/088468},
year = {2016}
}
Download

RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:label>1</jats:label><jats:title>Abstract</jats:title><jats:p>Azole antifungal drugs target<jats:italic>CYP51A</jats:italic>in<jats:italic>Aspergillus fumigatus</jats:italic>by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole anti-fungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, conferring resistance to itraconazole. In this study, we create a homology model of<jats:italic>CYP51A</jats:italic>using a recently published crystal structure of the paralog protein<jats:italic>CYP51B</jats:italic>. The derived structures, wild-type and L98H mutant, are positioned within a lipid membrane bilayer and subjected to molecular dynamics simulations in order improve the accuracy of both models. The structural analysis from our simulations suggests a decrease in active site surface from the formation of hydrogen bonds between the histidine substitution and neighbouring polar side chains, potentially preventing the binding of azole drugs. This study yields a biologically relevant structure and set dynamics of the<jats:italic>A. fumigatus</jats:italic>Lanosterol 14 alpha-demethylase enzyme and provides further insight into azole antifungal drug resistance.</jats:p>
AU  - Nash,A
AU  - Rhodes,J
DO  - 10.1101/088468
PY  - 2016///
TI  - Simulations of<i>CYP51A</i>from<i>Aspergillus fumigatus</i>in a model bilayer provide insights into triazole drug resistance
UR  - http://dx.doi.org/10.1101/088468
ER  -
Download