Open AccessSubstrate Recognition by a Colistin Resistance Enzyme from Moraxella catarrhalis
Author(s) -
P.J. Stogios,
Georgina Cox,
Haley L. Zubyk,
E. Evdokimova,
Z. Wawrzak,
Gerard D. Wright,
Alexei Savchenko
Publication year - 2018
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.8b00116
Subject(s) - moraxella catarrhalis , moraxella (branhamella) catarrhalis , microbiology and biotechnology , colistin , enzyme , substrate (aquarium) , moraxella , resistance (ecology) , bacteria , chemistry , biology , biochemistry , antibiotics , genetics , haemophilus influenzae , ecology
Lipid A phosphoethanolamine (PEtN) transferases render bacteria resistant to the last resort antibiotic colistin. The recent discoveries of pathogenic bacteria harboring plasmid-borne PEtN transferase ( mcr) genes have illustrated the serious potential for wide dissemination of these resistance elements. The origin of mcr-1 is traced to Moraxella species co-occupying environmental niches with Enterobacteriaceae. Here, we describe the crystal structure of the catalytic domain of the chromosomally encoded colistin resistance PEtN transferase, ICR Mc (for intrinsic colistin resistance) of Moraxella catarrhalis. The ICR Mc structure in complex with PEtN reveals key molecular details including specific residues involved in catalysis and PEtN binding. It also demonstrates that ICR Mc catalytic domain dimerization is required for substrate binding. Our structure-guided phylogenetic analysis provides sequence signatures defining potentially colistin-active representatives in this enzyme family. Combined, these results advance the molecular and mechanistic understanding of PEtN transferases and illuminate their origins.