6BNC

Crystal structure of the intrinsic colistin resistance enzyme ICR(Mc) from Moraxella catarrhalis, catalytic domain, Thr315Ala mutant di-zinc and PEG complex

6BNC の概要

• エントリーDOI: 10.2210/pdb6bnc/pdb
• 関連するPDBエントリー: 6BND 6BNE 6BNF
• 分子名称: Phosphoethanolamine transferase, ZINC ION, POLYETHYLENE GLYCOL (N=34), ... (5 entities in total)
• 機能のキーワード: antibiotic resistance, colistin, polymycin, phosphoethanolamine transferase, sulfatase fold, alpha/beta protein, structural genomics, center for structural genomics of infectious diseases, csgid, transferase
• 由来する生物種: Moraxella sp. HMSC061H09
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89948.25

構造登録者

Stogios, P.J.,Evdokimova, E.,Wawrzak, Z.,Savchenko, A.,Anderson, W.F.,Satchell, K.J.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2017-11-16, 公開日: 2018-01-31, 最終更新日: 2024-10-16)

主引用文献

Stogios, P.J.,Cox, G.,Zubyk, H.L.,Evdokimova, E.,Wawrzak, Z.,Wright, G.D.,Savchenko, A.
Substrate Recognition by a Colistin Resistance Enzyme from Moraxella catarrhalis.
ACS Chem. Biol., 13:1322-1332, 2018

PubMed 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 (for intrinsic colistin resistance) of Moraxella catarrhalis. The ICR structure in complex with PEtN reveals key molecular details including specific residues involved in catalysis and PEtN binding. It also demonstrates that ICR 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.

PubMed: 29631403
DOI: 10.1021/acschembio.8b00116

実験手法

X-RAY DIFFRACTION (1.5 Å)