Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/128573
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Biochemical characterisation of class III biotin protein ligases from Botrytis cinerea and Zymoseptoria tritici
Author: Sternicki, L.M.
Nguyen, S.
Pacholarz, K.J.
Barran, P.
Pendini, N.R.
Booker, G.W.
Huet, Y.
Baltz, R.
Wegener, K.L.
Pukala, T.L.
Polyak, S.W.
Citation: Archives of Biochemistry and Biophysics, 2020; 691:108509-1-108509-11
Publisher: Elsevier
Issue Date: 2020
ISSN: 0003-9861
1096-0384
Statement of
Responsibility: 
Louise M. Sternicki, Stephanie Nguyen, Kamila J. Pacholarz, Perdita Barran, Nicole R. Pendini, Grant W. Booker, Yoann Huet, Rachel Baltz, Kate L. Wegener, Tara L. Pukala, Steven W. Polyak
Abstract: Biotin protein ligase (BPL) is an essential enzyme in all kingdoms of life, making it a potential target for novel anti-infective agents. Whilst bacteria and archaea have simple BPL structures (class I and II), the homologues from certain eukaryotes such as mammals, insects and yeast (class III) have evolved a more complex structure with a large extension on the N-terminus of the protein in addition to the conserved catalytic domain. The absence of atomic resolution structures of any class III BPL hinders structural and functional analysis of these enzymes. Here, two new class III BPLs from agriculturally important moulds Botrytis cinerea and Zymoseptoria tritici were characterised alongside the homologue from the prototypical yeast Saccharomyces cerevisiae. Circular dichroism and ion mobility-mass spectrometry analysis revealed conservation of the overall tertiary and secondary structures of all three BPLs, corresponding with the high sequence similarity. Subtle structural differences were implied by the different thermal stabilities of the enzymes and their varied Michaelis constants for their interactions with ligands biotin, MgATP, and biotin-accepting substrates from different species. The three BPLs displayed different preferences for fungal versus bacterial protein substrates, providing further evidence that class III BPLs have a 'substrate validation' activity for selecting only appropriate proteins for biotinylation. Selective, potent inhibition of these three BPLs was demonstrated despite sequence and structural homology. This highlights the potential for targeting BPL for novel, selective antifungal therapies against B. cinerea, Z. tritici and other fungal species.
Keywords: Biotin; biotin protein ligase; fungal pathogens; Saccharomyces cerevisiae; Botrytis cinerea; Zymoseptoria tritici
Rights: © 2020 Elsevier Inc. All rights reserved.
RMID: 1000023957
DOI: 10.1016/j.abb.2020.108509
Grant ID: http://purl.org/au-research/grants/nhmrc/1147538
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.