title: The structural basis for T-antigen hydrolysis by Streptococcus pneumoniae: a target for structure-based vaccine design.
abstract: Streptococcus pneumoniae endo-alpha-N-acetylgalactosaminidase is a cell surface-anchored glycoside hydrolase from family GH101 involved in the breakdown of mucin type O-linked glycans. The 189-kDa mature enzyme specifically hydrolyzes the T-antigen disaccharide from extracellular host glycoproteins and is representative of a broadly important class of virulence factors that have remained structurally uncharacterized due to their large size and highly modular nature. Here we report a 2.9 angstroms resolution crystal structure that remarkably captures the multidomain architecture and characterizes a catalytic center unexpectedly resembling that of alpha-amylases. Our analysis presents a complete model of glycoprotein recognition and provides a basis for the structure-based design of novel Streptococcus vaccines and therapeutics.
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre for Blood Research and Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z3.
authors.forename: Matthew E C
authors.initials: ME
authors.lastname: Caines
authors.forename: Haizhong
authors.initials: H
authors.lastname: Zhu
authors.forename: Marija
authors.initials: M
authors.lastname: Vuckovic
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Willis
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
authors.forename: Warren W
authors.initials: WW
authors.lastname: Wakarchuk
authors.forename: Natalie C J
authors.initials: NC
authors.lastname: Strynadka
mesh_terms: D000957:Antigens, Viral, Tumor / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D006868:Hydrolysis; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D022541:Streptococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor; D022541:Streptococcal Vaccines