3ZGP

NMR structure of the catalytic domain from E. faecium L,D- transpeptidase acylated by ertapenem

3ZGP の概要

• エントリーDOI: 10.2210/pdb3zgp/pdb
• 関連するPDBエントリー: 3ZG4
• NMR情報: BMRB: 18911
• 分子名称: ERFK/YBIS/YCFS/YNHG, (4R,5S)-3-({(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl}sulfanyl)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid (2 entities in total)
• 機能のキーワード: transferase, transpeptidation, peptidoglycan biosynthesis, antibiotic resistance
• 由来する生物種: ENTEROCOCCUS FAECIUM
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15049.68

構造登録者

Lecoq, L.,Triboulet, S.,Dubee, V.,Bougault, C.,Hugonnet, J.E.,Arthur, M.,Simorre, J.P. (登録日: 2012-12-18, 公開日: 2013-04-24, 最終更新日: 2024-11-06)

主引用文献

Lecoq, L.,Triboulet, S.,Dubee, V.,Bougault, C.,Hugonnet, J.E.,Arthur, M.,Simorre, J.P.
The Structure of Enterococcus Faecium L,D---Transpeptidase Acylated by Ertapenem Provides Insight Into the Inactivation Mechanism.
Acs Chem.Biol., 8:1140-1146, 2013

PubMed Abstract: The maintenance of bacterial cell shape and integrity is largely attributed to peptidoglycan, a biopolymer highly cross-linked through d,d-transpeptidation. Peptidoglycan cross-linking is catalyzed by penicillin-binding proteins (PBPs) that are the essential target of β-lactam antibiotics. PBPs are functionally replaced by l,d-transpeptidases (Ldts) in ampicillin-resistant mutants of Enterococcus faecium and in wild-type Mycobacterium tuberculosis. Ldts are inhibited in vivo by a single class of β-lactams, the carbapenems, which act as a suicide substrate. We present here the first structure of a carbapenem-acylated l,d-transpeptidase, E. faecium Ldtfm acylated by ertapenem, which revealed key contacts between the carbapenem core and residues of the catalytic cavity of the enzyme. Significant reorganization of the antibiotic conformation occurs upon enzyme acylation. These results, together with the analysis of protein-to-carbapenem proton transfers, provide new insights into the mechanism of Ldt acylation by carbapenems.

PubMed: 23574509
DOI: 10.1021/cb4001603

実験手法

SOLUTION NMR