1. Molecular Basis of Mannose Recognition by Pradimicins and their Application to Microbial Cell Surface Imaging
- Author
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Misako Aida, Tomohiko Tomura, Daisuke Hashizume, Yukishige Ito, Takashi Doi, Yasuhiro Igarashi, Kazue Tsuzuki, Kiyonori Takegoshi, Dai Akase, Yu Nakagawa, Makoto Ojika, Takahiro Sugahara, and Yasunori Watanabe
- Subjects
Magnetic Resonance Spectroscopy ,Fluorophore ,Dimer ,Clinical Biochemistry ,Mannose ,Biology ,Crystallography, X-Ray ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Molecular recognition ,Drug Discovery ,Humans ,Anthracyclines ,Molecular Biology ,Binding selectivity ,Pharmacology ,Binding Sites ,010405 organic chemistry ,Cell Membrane ,Lectin ,Nuclear magnetic resonance spectroscopy ,Small molecule ,0104 chemical sciences ,Actinobacteria ,chemistry ,Biophysics ,biology.protein ,Molecular Medicine ,Dimerization - Abstract
Naturally occurring pradimicins (PRMs) show specific recognition of d-mannose (d-Man) in aqueous media, which has never been achieved by artificial small molecules. Although the Ca2+-mediated dimerization of PRMs is essential for their d-Man binding, the dimeric structure has yet to be elucidated, leaving the question open as to how PRMs recognize d-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 the d-Man binding geometry of PRMs, elucidation of the dimer allowed reliable estimation of the mode of d-Man binding. Based on the binding model, we further developed an azide-functionalized PRM derivative (PRM-Azide) with d-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., ファイル公開：2020-07-18
- Published
- 2019
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