title: Structural studies of an anti-inflammatory lectin from Canavalia boliviana seeds in complex with dimannosides.
abstract: Plant lectins, especially those purified from species of the Leguminosae family, represent the best-studied group of carbohydrate-binding proteins. Lectins purified from seeds of the Diocleinae subtribe exhibit a high degree of sequence identity notwithstanding that they show very distinct biological activities. Two main factors have been related to this feature: variance in key residues influencing the carbohydrate-binding site geometry and differences in the pH-dependent oligomeric state profile. In this work, we have isolated a lectin from Canavalia boliviana (Cbol) and solved its x-ray crystal structure in the unbound form and in complex with the carbohydrates Man(α1-3)Man(α1-O)Me, Man(α1-4)Man(α1-O)Me and 5-bromo-4-chloro-3-indolyl-α-D-mannose. We evaluated its oligomerization profile at different pH values using Small Angle X-ray Scattering and compared it to that of Concanavalin A. Based on predicted pKa-shifts of amino acids in the subunit interfaces we devised a model for the dimer-tetramer equilibrium phenomena of these proteins. Additionally, we demonstrated Cbol anti-inflammatory properties and further characterized them using in vivo and in vitro models.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Gustavo Arruda
authors.initials: GA
authors.lastname: Bezerra
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Viertlmayr
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Tales Rocha
authors.initials: TR
authors.lastname: Moura
authors.affiliation: Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Brazil.
authors.forename: Plínio
authors.initials: P
authors.lastname: Delatorre
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Bruno Anderson Matias
authors.initials: BA
authors.lastname: Rocha
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Kyria Santiago
authors.initials: KS
authors.lastname: do Nascimento
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Jozi Godoy
authors.initials: JG
authors.lastname: Figueiredo
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Ingrid Gonçalves
authors.initials: IG
authors.lastname: Bezerra
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Cicero Silvano
authors.initials: CS
authors.lastname: Teixeira
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Rafael Conceição
authors.initials: RC
authors.lastname: Simões
authors.affiliation: Department of Fishing Engineering, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Celso Shiniti
authors.initials: CS
authors.lastname: Nagano
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Nylane Maria Nunes
authors.initials: NM
authors.lastname: de Alencar
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Gruber
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Benildo Sousa
authors.initials: BS
authors.lastname: Cavada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001665:Binding Sites; D032449:Canavalia / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D018360:Crystallography, X-Ray; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D008362:Mannosides / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy*; D037121:Plant Lectins / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000893:Anti-Inflammatory Agents; D008362:Mannosides; D037121:Plant Lectins