Structural Characterisation of the Beta-Ketoacyl-Acyl Carrier Protein Synthases, FabF and FabH, of Yersinia pestis
View/ Open
File version
Version of Record (VoR)
Author(s)
Nanson, Jeffrey D
Himiari, Zainab
Swarbrick, Crystall MD
Forwood, Jade K
Griffith University Author(s)
Year published
2015
Metadata
Show full item recordAbstract
Yersinia pestis, the causative agent of bubonic, pneumonic and septicaemic plague, remains a major public health threat, with outbreaks of disease occurring in China, Madagascar and Peru in the last five years. The existence of multidrug resistant Y. pestis and the potential of this bacterium as a bioterrorism agent illustrates the need for new antimicrobials. The β-ketoacyl-acyl carrier protein synthases, FabB, FabF and FabH, catalyse the elongation of fatty acids as part of the type II fatty acid biosynthesis (FASII) system, to synthesise components of lipoproteins, phospholipids and lipopolysaccharides essential for ...
View more >Yersinia pestis, the causative agent of bubonic, pneumonic and septicaemic plague, remains a major public health threat, with outbreaks of disease occurring in China, Madagascar and Peru in the last five years. The existence of multidrug resistant Y. pestis and the potential of this bacterium as a bioterrorism agent illustrates the need for new antimicrobials. The β-ketoacyl-acyl carrier protein synthases, FabB, FabF and FabH, catalyse the elongation of fatty acids as part of the type II fatty acid biosynthesis (FASII) system, to synthesise components of lipoproteins, phospholipids and lipopolysaccharides essential for bacterial growth and survival. As such, these enzymes are promising targets for the development of novel therapeutic agents. We have determined the crystal structures of the Y. pestis β-ketoacyl-acyl carrier protein synthases FabF and FabH and compared these with the unpublished, deposited structure of Y. pestis FabB. Comparison of FabB, FabF and FabH provides insights into the substrate specificities of these enzymes and investigation of possible interactions with known β-ketoacyl-acyl carrier protein synthase inhibitors suggests FabB, FabF and FabH may be targeted simultaneously to prevent synthesis of the fatty acids necessary for growth and survival.
View less >
View more >Yersinia pestis, the causative agent of bubonic, pneumonic and septicaemic plague, remains a major public health threat, with outbreaks of disease occurring in China, Madagascar and Peru in the last five years. The existence of multidrug resistant Y. pestis and the potential of this bacterium as a bioterrorism agent illustrates the need for new antimicrobials. The β-ketoacyl-acyl carrier protein synthases, FabB, FabF and FabH, catalyse the elongation of fatty acids as part of the type II fatty acid biosynthesis (FASII) system, to synthesise components of lipoproteins, phospholipids and lipopolysaccharides essential for bacterial growth and survival. As such, these enzymes are promising targets for the development of novel therapeutic agents. We have determined the crystal structures of the Y. pestis β-ketoacyl-acyl carrier protein synthases FabF and FabH and compared these with the unpublished, deposited structure of Y. pestis FabB. Comparison of FabB, FabF and FabH provides insights into the substrate specificities of these enzymes and investigation of possible interactions with known β-ketoacyl-acyl carrier protein synthase inhibitors suggests FabB, FabF and FabH may be targeted simultaneously to prevent synthesis of the fatty acids necessary for growth and survival.
View less >
Journal Title
Scientific Reports
Volume
5
Issue
1
Copyright Statement
© The Author(s) 2015. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Subject
Biochemistry and Cell Biology
Other Physical Sciences
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CRYSTAL-STRUCTURE
SUBSTRATE-SPECIFICITY