title: High mannose-binding lectin with preference for the cluster of alpha1-2-mannose from the green alga Boodlea coacta is a potent entry inhibitor of HIV-1 and influenza viruses.
abstract: The complete amino acid sequence of a lectin from the green alga Boodlea coacta (BCA), which was determined by a combination of Edman degradation of its peptide fragments and cDNA cloning, revealed the following: 1) B. coacta used a noncanonical genetic code (where TAA and TAG codons encode glutamine rather than a translation termination), and 2) BCA consisted of three internal tandem-repeated domains, each of which contains the sequence motif similar to the carbohydrate-binding site of Galanthus nivalis agglutinin-related lectins. Carbohydrate binding specificity of BCA was examined by a centrifugal ultrafiltration-HPLC assay using 42 pyridylaminated oligosaccharides. BCA bound to high mannose-type N-glycans but not to the complex-type, hybrid-type core structure of N-glycans or oligosaccharides from glycolipids. This lectin had exclusive specificity for α1-2-linked mannose at the nonreducing terminus. The binding activity was enhanced as the number of terminal α1-2-linked mannose substitutions increased. Mannobiose, mannotriose, and mannopentaose were incapable of binding to BCA. Thus, BCA preferentially recognized the nonreducing terminal α1-2-mannose cluster as a primary target. As predicted from carbohydrate-binding propensity, this lectin inhibited the HIV-1 entry into the host cells at a half-maximal effective concentration of 8.2 nm. A high association constant (3.71 × 10(8) M(-1)) of BCA with the HIV envelope glycoprotein gp120 was demonstrated by surface plasmon resonance analysis. Moreover, BCA showed the potent anti-influenza activity by directly binding to viral envelope hemagglutinin against various strains, including a clinical isolate of pandemic H1N1-2009 virus, revealing its potential as an antiviral reagent.
authors: Faculty of Pharmacy, Yasuda Women's University, Asaminami, Hiroshima, Japan.
authors: Yuichiro
authors: Y
authors: Sato
authors: Makoto
authors: M
authors: Hirayama
authors: Kinjiro
authors: K
authors: Morimoto
authors: Naoki
authors: N
authors: Yamamoto
authors: Satomi
authors: S
authors: Okuyama
authors: Kanji
authors: K
authors: Hori
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000460:Chlorophyta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008358:Mannose / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D015699:HIV Envelope Protein gp120; D037241:Mannose-Binding Lectins; D010940:Plant Proteins; D008358:Mannose