Title

Structure-based discovery of a small-molecule inhibitor of methicillin-resistant

Document Type

Article

Publication Date

3-16-2020

Keywords

JGM

JAX Source

J Biol Chem 2020 Mar 16 [Epub ahead of print]

PMID

32179646

DOI

https://doi.org/10.1074/jbc.RA120.012697

Abstract

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton-Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C

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