The structural basis for T-antigen hydrolysis by Streptococcus pneumoniae: a target for structure-based vaccine design.
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.
Caines
Matthew E C
ME
Department of Biochemistry and Molecular Biology, Centre for Blood Research and Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z3.
Zhu
Haizhong
H
Vuckovic
Marija
M
Willis
Lisa M
LM
Withers
Stephen G
SG
Wakarchuk
Warren W
WW
Strynadka
Natalie C J
NC
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
D000957:Antigens, Viral, Tumor; D022541:Streptococcal Vaccines