title: A Multivalent Marine Lectin from Crenomytilus grayanus Possesses Anti-cancer Activity through Recognizing Globotriose Gb3.
abstract: In this study, we report the structure and function of a lectin from the sea mollusk Crenomytilus grayanus collected from the sublittoral zone of Peter the Great Bay of the Sea of Japan. The crystal structure of C. grayanus lectin (CGL) was solved to a resolution of 1.08 Å, revealing a β-trefoil fold that dimerizes into a dumbbell-shaped quaternary structure. Analysis of the crystal CGL structures bound to galactose, galactosamine, and globotriose Gb3 indicated that each CGL can bind three ligands through a carbohydrate-binding motif involving an extensive histidine- and water-mediated hydrogen bond network. CGL binding to Gb3 is further enhanced by additional side-chain-mediated hydrogen bonds in each of the three ligand-binding sites. NMR titrations revealed that the three binding sites have distinct microscopic affinities toward galactose and galactosamine. Cell viability assays showed that CGL recognizes Gb3 on the surface of breast cancer cells, leading to cell death. Our findings suggest the use of this lectin in cancer diagnosis and treatment.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Jiahn-Haur
authors.initials: JH
authors.lastname: Liao
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.|Department of Chemistry, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Chih-Ta Henry
authors.initials: CT
authors.lastname: Chien
authors.affiliation: Institute of Biological Chemistry, Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica , Taipei 115, Taiwan.|Department of Chemistry, National Tsing Hua University , Hsinchu 30043, Taiwan.
authors.forename: Han-Ying
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Kai-Fa
authors.initials: KF
authors.lastname: Huang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Iren
authors.initials: I
authors.lastname: Wang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Ho
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: I-Fan
authors.initials: IF
authors.lastname: Tu
authors.affiliation: Institute of Biochemical Science, National Taiwan University , Taipei 106, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Key Laboratory of Aquatic Products Processing and Utilization of Liaoning Province, Dalian Ocean University , Dalian 116023, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Shih
authors.affiliation: Genomics Research Center, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences , Vladivostok 690022, Russian Federation.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Lukyanov
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.|Institute of Biological Chemistry, Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica , Taipei 115, Taiwan.|Institute of Biochemical Science, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Shang-Te Danny
authors.initials: ST
authors.lastname: Hsu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica , Taipei 11529, Taiwan.|Department of Chemistry, National Taiwan University , Taipei 106, Taiwan.|Institute of Biological Chemistry, Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica , Taipei 115, Taiwan.|Institute of Biochemical Science, National Taiwan University , Taipei 106, Taiwan.
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D049872:Bivalvia / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002240:Carbohydrate Sequence; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D061986:MCF-7 Cells; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D014312:Trisaccharides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D037102:Lectins; D014312:Trisaccharides; C113460:globotriose