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Int J Mol Sci. 2019 Mar 15;20(6). pii: E1304. doi: 10.3390/ijms20061304.

Effect of A22 on the Conformation of Bacterial Actin MreB.

Author information

1
Department of Biochemistry, School of Biological Sciences, CANS, University of Cape Coast, Cape Coast 00233, Ghana. elvis.awuni@ucc.edu.gh.
2
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. ygmu@ntu.edu.sg.

Abstract

The mechanism of the antibiotic molecule A22 is yet to be clearly understood. In a previous study, we carried out molecular dynamics simulations of a monomer of the bacterial actin-like MreB in complex with different nucleotides and A22, and suggested that A22 impedes the release of Pi from the active site of MreB after the hydrolysis of ATP, resulting in filament instability. On the basis of the suggestion that Pi release occurs on a similar timescale to polymerization and that polymerization can occur in the absence of nucleotides, we sought in this study to investigate a hypothesis that A22 impedes the conformational change in MreB that is required for polymerization through molecular dynamics simulations of the MreB protofilament in the apo, ATP+, and ATP-A22+ states. We suggest that A22 inhibits MreB in part by antagonizing the ATP-induced structural changes required for polymerization. Our data give further insight into the polymerization/depolymerization dynamics of MreB and the mechanism of A22.

KEYWORDS:

actin-like MreB; conformational change; depolymerization; molecular dynamics; polymerization; simulations

PMID:
30875875
PMCID:
PMC6471442
DOI:
10.3390/ijms20061304
[Indexed for MEDLINE]
Free PMC Article

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