Structural Basis for T-antigen Hydrolysis by Streptococcus pneumoniae: A TARGET FOR STRUCTURE-BASED VACCINE DESIGN

Streptococcus pneumoniae endo-α-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...

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Veröffentlicht in:The Journal of biological chemistry 2008-11, Vol.283 (46), p.31279-31283
Hauptverfasser: Caines, Matthew E.C, Zhu, Haizhong, Vuckovic, Marija, Willis, Lisa M, Withers, Stephen G, Wakarchuk, Warren W, Strynadka, Natalie C.J
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container_end_page 31283
container_issue 46
container_start_page 31279
container_title The Journal of biological chemistry
container_volume 283
creator Caines, Matthew E.C
Zhu, Haizhong
Vuckovic, Marija
Willis, Lisa M
Withers, Stephen G
Wakarchuk, Warren W
Strynadka, Natalie C.J
description Streptococcus pneumoniae endo-α-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 Å resolution crystal structure that remarkably captures the multidomain architecture and characterizes a catalytic center unexpectedly resembling that of α-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.
doi_str_mv 10.1074/jbc.C800150200
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subjects Antigens, Viral, Tumor - chemistry
Antigens, Viral, Tumor - immunology
Antigens, Viral, Tumor - metabolism
Catalytic Domain
Crystallography, X-Ray
Drug Design
Hydrolysis
Models, Molecular
Protein Structure, Tertiary
Streptococcal Vaccines - immunology
Streptococcus pneumoniae - chemistry
Streptococcus pneumoniae - immunology
Streptococcus pneumoniae - metabolism
title Structural Basis for T-antigen Hydrolysis by Streptococcus pneumoniae: A TARGET FOR STRUCTURE-BASED VACCINE DESIGN
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