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  • Potent DNA gyrase inhibitors bind asymmetrically to their target using symmetrical bifurcated halogen bonds [Elektronski vir]
    Kolarič, Anja, farmacevtka ...
    Novel bacterial type II topoisomerase inhibitors (NBTIs) stabilize single-strand DNA cleavage breaks by DNA gyrase but their exact mechanism of action has remained hypothetical until now. We have ... designed a small library of NBTIs with an improved DNA gyrase-binding moiety resulting in low nanomolar inhibition and very potent antibacterial activity. They stabilize single-stranded cleavage complexes and, importantly, we have obtained the crystal structure where an NBTI binds gyrase-DNA in a single conformation lacking apparent static disorder. This directly proves the previously postulated NBTI mechanism of action and shows that they stabilize single-strand cleavage through asymmetric intercalation with a shift of the scissile phosphate. This crystal stucture shows that the chlorine forms a halogen bond with the backbone carbonyls of the two symmetry-related Ala68 residues. To the best of our knowledge, such a so-called symmetrical bifurcated halogen bond has not been identified in a biological system until now.
    Source: Nature communications [Elektronski vir]. - ISSN 2041-1723 (Vol. 12, 8 Jan. 2021, str. 150-1-150-13)
    Type of material - e-article
    Publish date - 2021
    Language - english
    COBISS.SI-ID - 46272259

    Link(s):

    https://www.nature.com/articles/s41467-020-20405-8
    Repository of the University of Ljubljana – RUL
    DOI

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