Structural and mechanistic analysis of ATPase inhibitors targeting mycobacterial DNA gyrase.

ABSTRACT:

Objectives

To evaluate the efficacy of two novel compounds against mycobacteria and determine the molecular basis of their action on DNA gyrase using structural and mechanistic approaches.

Methods

Redx03863 and Redx04739 were tested in antibacterial assays, and also against their target, DNA gyrase, using DNA supercoiling and ATPase assays. X-ray crystallography was used to determine the structure of the gyrase B protein ATPase sub-domain from Mycobacterium smegmatis complexed with the aminocoumarin drug novobiocin, and structures of the same domain from Mycobacterium thermoresistibile complexed with novobiocin, and also with Redx03863.

Results

Both compounds, Redx03863 and Redx04739, were active against selected Gram-positive and Gram-negative species, with Redx03863

SUBMITTER: Henderson SR 

PROVIDER: S-EPMC7556816 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature