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

被引：40

作者：

Caines, Matthew E. C. ^{[1
,2
]}

Zhu, Haizhong ^{[1
,2
]}

Vuckovic, Marija ^{[1
,2
]}

Willis, Lisa M. ^{[4
]}

Withers, Stephen G. ^{[1
,3
]}

Wakarchuk, Warren W. ^{[4
]}

Strynadka, Natalie C. J. ^{[1
,2
]}

机构：

[1] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada

[2] Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada

[3] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z3, Canada

[4] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 46期

基金：

加拿大创新基金会; 加拿大健康研究院;

关键词：

D O I：

10.1074/jbc.C800150200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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 angstrom 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.

引用

页码：31279 / 31283

页数：5

共 48 条

[1]

Complexes of Thermoactinomyces vulgaris R-47 α-amylase 1 and pullulan model oligossacharides provide new insight into the mechanism for recognizing substrates with α-(1,6) glycosidic linkages [J].

Abe, A ;

Yoshida, H ;

Tonozuka, T ;

Sakano, Y ;

Kamitori, S .

FEBS JOURNAL, 2005, 272 (23) :6145-6153

[2]

Methods used in the structure determination of bovine mitochondrial F-1 ATPase [J].

Abrahams, JP ;

Leslie, AGW .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1996, 52 :30-42

[3]

Global antibiotic resistance in Streptococcus pneumoniae [J].

Adam, D .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2002, 50 :1-5

[4]

[Anonymous], 2005, CCP4 Newsletter

[5]

Molecular basis for the selectivity and specificity of ligand recognition by the family 16 carbohydrate-binding modules from Thermoanaerobacterium polysaccharolyticum ManA [J].

Bae, Brian ;

Ohene-Adjei, Samuel ;

Kocherginskaya, Svetlana ;

Mackie, Roderick I. ;

Spies, M. Ashley ;

Cann, Isaac K. O. ;

Nair, Satish K. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (18) :12415-12425

[6]

THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[7]

Electrostatics of nanosystems: Application to microtubules and the ribosome [J].

Baker, NA ;

Sept, D ;

Joseph, S ;

Holst, MJ ;

McCammon, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10037-10041

[8]

Streptococcus pneumoniae colonisation:: the key to pneumococcal disease [J].

Bogaert, D ;

de Groot, R ;

Hermans, PWM .

LANCET INFECTIOUS DISEASES, 2004, 4 (03) :144-154

[9]

Pneumococcal vaccines:: an update on current strategies [J].

Bogaert, D ;

Hermans, PWM ;

Adrian, PV ;

Rümke, HC ;

de Groot, R .

VACCINE, 2004, 22 (17-18) :2209-2220

[10]

Differential oligosaccharide recognition by evolutionarily-related β-1,4 and β-1,3 glucan-binding modules [J].

Boraston, AB ;

Nurizzo, D ;

Notenboom, V ;

Ducros, V ;

Rose, DR ;

Kilburn, DG ;

Davies, GJ .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 319 (05) :1143-1156

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