title: Pradimicin A, a D-mannose-binding antibiotic, binds pyranosides of L-fucose and L-galactose in a calcium-sensitive manner.
abstract: Pradimicin A (PRM-A) is a unique antibiotic with a lectin-like ability to bind D-mannose (D-Man) in the presence of Ca(2+) ion. Although accumulated evidences suggest that PRM-A recognizes the 2-, 3-, and 4-hydroxyl groups of D-Man, BMY-28864, an artificial PRM-A derivative, was shown not to bind L-fucose (L-Fuc) and L-galactose (lLGal), both of which share the characteristic array of the three hydroxyl groups with D-Man. To obtain a plausible explanation for this inconsistency, we performed co-precipitation experiments of PRM-A with L-Fuc, L-Gal, and their methyl pyranosides (L-Fuc-OMe, L-Gal-OMe) by taking advantage of aggregate-forming propensity of the binary [PRM-A/Ca(2+)] complex. While L-Fuc and L-Gal were hardly incorporated into the aggregate, L-Fuc-OMe and L-Gal-OMe were found to exhibit significant binding to PRM-A. However, increased Ca(2+) concentration abolished this binding, raising the possibility that poor binding of L-Fuc and L-Gal to PRM-A is attributed to their chelation with Ca(2+) ion. This possibility was partly supported by (1)H NMR analysis that detected interaction of L-Fuc and L-Gal with Ca(2+) ion in aqueous solution. These results collectively indicate that PRM-A binds pyranosides of L-Fuc and L-Gal when Ca(2+) concentration is not excessive to trap these sugars by chelation but sufficient to form the [PRM-A/Ca(2+)] complex.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: yu@agr.nagoya-u.ac.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Japan Science and Technology Agency, ERATO, Ito Glycotrilogy Project, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D005643:Fucose / Q000737:chemistry / Q000378:metabolism*; D005690:Galactose / Q000737:chemistry / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry / Q000378:metabolism*; D000095643:Pradimicins and Benanomicins
chemical_list: D018943:Anthracyclines; D000900:Anti-Bacterial Agents; D002118:Calcium; D005643:Fucose; D005690:Galactose; D006027:Glycosides; D008358:Mannose; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins
keywords: Antibiotic; Carbohydrate recognition; Lectin; Natural product; Pradimicin