Resistance to the "last resort" antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes. Issue 50 (20th May 2020)

• Record Type: Journal Article
• Authors: Lythell, Emily; Suardíaz, Reynier; Hinchliffe, Philip; Hanpaibool, Chonnikan; Visitsatthawong, Surawit; Oliveira, A. Sofia F.; Lang, Eric J. M.; Surawatanawong, Panida; Lee, Vannajan Sanghiran; Rungrotmongkol, Thanyada; Fey, Natalie; Spencer, James; Mulholland, Adrian J.
• Is Part Of: Chemical communications. Volume 56:Issue 50(2020)
• Page Start: 6874
• Page End: 6877
• Publication Date: 2020-05-20
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc02520h
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Simulations show the mono-zinc form of MCR to be stable and competent for covalent phospho(ethanolamine) intermediate formation. Abstract : MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the "last-resort" antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.