5HL9

E. coli PBP1b in complex with acyl-ampicillin and moenomycin

5HL9 の概要

• エントリーDOI: 10.2210/pdb5hl9/pdb
• 関連するPDBエントリー: 5HLA 5HLB 5HLD
• 分子名称: Penicillin-binding protein 1B, (2R,4S)-2-[(1R)-1-{[(2R)-2-amino-2-phenylacetyl]amino}-2-oxoethyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, MOENOMYCIN, ... (4 entities in total)
• 機能のキーワード: penicillin-binding protein, inhibitor complex, transpeptidase, transglycosylase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 85212.34

構造登録者

King, D.T.,Strynadka, N.C.J. (登録日: 2016-01-14, 公開日: 2016-12-14, 最終更新日: 2024-10-16)

主引用文献

King, D.T.,Wasney, G.A.,Nosella, M.,Fong, A.,Strynadka, N.C.
Structural Insights into Inhibition of Escherichia coli Penicillin-binding Protein 1B.
J.Biol.Chem., 292:979-993, 2017

PubMed Abstract: In Escherichia coli, the peptidoglycan cell wall is synthesized by bifunctional penicillin-binding proteins such as PBP1b that have both transpeptidase and transglycosylase activities. The PBP1b transpeptidase domain is a major target of β-lactams, and therefore it is important to attain a detailed understanding of its inhibition. The peptidoglycan glycosyltransferase domain of PBP1b is also considered an excellent antibiotic target yet is not exploited by any clinically approved antibacterials. Herein, we adapt a pyrophosphate sensor assay to monitor PBP1b-catalyzed glycosyltransfer and present an improved crystallographic model for inhibition of the PBP1b glycosyltransferase domain by the potent substrate analog moenomycin. We elucidate the structure of a previously disordered region in the glycosyltransferase active site and discuss its implications with regards to peptidoglycan polymerization. Furthermore, we solve the crystal structures of E. coli PBP1b bound to multiple different β-lactams in the transpeptidase active site and complement these data with gel-based competition assays to provide a detailed structural understanding of its inhibition. Taken together, these biochemical and structural data allow us to propose new insights into inhibition of both enzymatic domains in PBP1b.

PubMed: 27899450
DOI: 10.1074/jbc.M116.718403

実験手法

X-RAY DIFFRACTION (2.7 Å)