Molecular Basis of Mannose Recognition by Pradimicins and their Application to Microbial Cell Surface Imaging. Issue 7 (18th July 2019)

• Record Type: Journal Article
• Authors: Nakagawa, Yu; Doi, Takashi; Takegoshi, K.; Sugahara, Takahiro; Akase, Dai; Aida, Misako; Tsuzuki, Kazue; Watanabe, Yasunori; Tomura, Tomohiko; Ojika, Makoto; Igarashi, Yasuhiro; Hashizume, Daisuke; Ito, Yukishige
• Is Part Of: Cell chemical biology. Volume 26:Issue 7(2019)
• Page Start: 950
• Page End: 959.e8
• Publication Date: 2019-07-18
• Subjects: analog design -- carbohydrates -- glycan detection -- lectin -- molecular recognition -- natural products -- structural elucidation; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2019.03.013
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Naturally occurring pradimicins (PRMs) show specific recognition ofd -mannose (d -Man) in aqueous media, which has never been achieved by artificial small molecules. Although the Ca 2+ -mediated dimerization of PRMs is essential for theird -Man binding, the dimeric structure has yet to be elucidated, leaving the question open as to how PRMs recognized -Man. Thus, we herein report the structural elucidation of the dimer by a combination of X-ray crystallography and solid-state NMR spectroscopy. Coupled with our previous knowledge regarding thed -Man binding geometry of PRMs, elucidation of the dimer allowed reliable estimation of the mode ofd -Man binding. Based on the binding model, we further developed an azide-functionalized PRM derivative (PRM-Azide) withd -Man binding specificity. Notably, PRM-Azide stained Candida rugosa cells having mannans on their cell surface through conjugation with the tetramethylrhodamine fluorophore. The present study provides the practical demonstration that PRMs can serve as lectin mimics for use in glycobiological studies. Graphical Abstract: Highlights: Dimeric structure of pradimicin (PRM) with mannose binding ability is elucidated NMR-based calculations provide a reliable binding model of PRM with mannose Azide-functionalized PRM (PRM-Azide) shows mannose binding specificity in water PRM-azide fluorescently stains cell wall mannans of Candida rugosa Abstract : Nakagawa et al. report the structural elucidation of pradimicin (PRM) dimer, and provide a possible answer as to how PRM recognizes mannose (Man). They also disclose that an azide-functionalized PRM retains mannose binding specificity in water, and fluorescently stains cell wall mannans of Candida rugosa .