PDBsum entry 6bnc

Transferase

PDB id: 6bnc

Contents

Protein chains

335 a.a.

Ligands

15P ×9

Metals

_CL

_ZN ×4

Waters ×1093

References listed in PDB file

Key reference

• Title: Substrate recognition by a colistin resistance enzyme from moraxella catarrhalis.
• Authors: P.J.Stogios, G.Cox, H.L.Zubyk, E.Evdokimova, Z.Wawrzak, G.D.Wright, A.Savchenko.
• Ref.: ACS Chem Biol, 2018, 13, 1322-1332. [DOI no: 10.1021/acschembio.8b00116]
• PubMed id: 29631403

Abstract

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.