GP0.4 from bacteriophage T7: in silico characterisation of its structure and interaction with E. coli FtsZ.

Simpkin, Adam J ORCID: 0000-0003-1883-9376 and Rigden, Daniel J ORCID: 0000-0002-7565-8937 (2016) GP0.4 from bacteriophage T7: in silico characterisation of its structure and interaction with E. coli FtsZ. BMC research notes, 9 (1). 343-.

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Abstract

<h4>Background</h4>Proteins produced by bacteriophages can have potent antimicrobial activity. The study of phage-host interactions can therefore inform small molecule drug discovery by revealing and characterising new drug targets. Here we characterise in silico the predicted interaction of gene protein 0.4 (GP0.4) from the Escherichia coli (E. coli) phage T7 with E. coli filamenting temperature-sensitive mutant Z division protein (FtsZ). FtsZ is a tubulin homolog which plays a key role in bacterial cell division and that has been proposed as a drug target.<h4>Results</h4>Using ab initio, fragment assembly structure modelling, we predicted the structure of GP0.4 with two programs. A structure similarity-based network was used to identify a U-shaped helix-turn-helix candidate fold as being favoured. ClusPro was used to dock this structure prediction to a homology model of E. coli FtsZ resulting in a favourable predicted interaction mode. Alternative docking methods supported the proposed mode which offered an immediate explanation for the anti-filamenting activity of GP0.4. Importantly, further strong support derived from a previously characterised insertion mutation, known to abolish GP0.4 activity, that is positioned in close proximity to the proposed GP0.4/FtsZ interface.<h4>Conclusions</h4>The mode of interaction predicted by bioinformatics techniques strongly suggests a mechanism through which GP0.4 inhibits FtsZ and further establishes the latter's druggable intrafilament interface as a potential drug target.

Item Type:	Article
Uncontrolled Keywords:	Escherichia coli, Bacteriophage T7, Bacterial Proteins, Cytoskeletal Proteins, Viral Proteins, Sequence Alignment, Gene Expression, Binding Sites, Amino Acid Sequence, Protein Structure, Secondary, Protein Binding, Protein Folding, Drug Design, Protein Interaction Domains and Motifs, Molecular Docking Simulation
Depositing User:	Symplectic Admin
Date Deposited:	13 Jul 2016 15:57
Last Modified:	19 Jan 2023 07:33
DOI:	10.1186/s13104-016-2149-5
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3002313