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Functional analysis of a group A streptococcal glycoside hydrolase Spy1600 from family 84 reveals it is a beta-N-acetylglucosaminidase and not a hyaluronidase

Academic Article
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Overview

authors

  • Sheldon, W. L.
  • Macauley, Matthew
  • Taylor, E. J.
  • Robinson, C. E.
  • Charnock, S. J.
  • Davies, G. J.
  • Vocadlo, D. J.
  • Black, G. W.

publication date

  • October 2006

journal

  • Biochemical Journal  Journal

abstract

  • Group A streptococcus (Streptococcus pyogenes) is the causative agent of severe invasive infections such as necrotizing fasciitis (the so-called 'flesh eating disease') and toxic-shock syndrome. Spy1600, a glycoside hydrolase from family 84 of the large superfamily of glycoside hydrolases, has been proposed to be a virulence factor. In the present study we show that Spy1600 has no activity toward galactosaminides or hyaluronan, but does remove beta-O-linked N-acetylglucosamine from mammalian glycoproteins--an observation consistent with the inclusion of eukaryotic O-glycoprotein 2-acetamido-2-deoxy-beta-D-glucopyranosidases within glycoside hydrolase family 84. Proton NMR studies, structure-reactivity studies for a series of fluorinated analogues and analysis of 1,2-dideoxy-2'-methyl-alpha-D-glucopyranoso-[2,1-d]-Delta2'-thiazoline as a competitive inhibitor reveals that Spy1600 uses a double-displacement mechanism involving substrate-assisted catalysis. Family 84 glycoside hydrolases are therefore comprised of both prokaryotic and eukaryotic beta-N-acetylglucosaminidases using a conserved catalytic mechanism involving substrate-assisted catalysis. Since these enzymes do not have detectable hyaluronidase activity, many family 84 glycoside hydrolases are most likely incorrectly annotated as hyaluronidases.

subject areas

  • Acetylglucosamine
  • Acetylglucosaminidase
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Catalysis
  • Cercopithecus aethiops
  • Escherichia coli
  • Histone Acetyltransferases
  • Humans
  • Hyaluronoglucosaminidase
  • Hydrolysis
  • Hymecromone
  • Kinetics
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Nuclear Magnetic Resonance, Biomolecular
  • Sequence Homology, Amino Acid
  • Streptococcus pyogenes
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thiazoles
  • beta-N-Acetylhexosaminidases
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Research

keywords

  • 1,2-dideoxy-2 '-methyl-alpha-D-glucopyranoso-[2,1-d]-Delta 2 '-thiazoline (NAG-thiazoline)
  • O-glycoprotein 2-acetamido-2-deoxy-beta-D-glucopyranosidase (O-GIcNAcase)
  • O-glycoprotein 2-acetamido-2-deoxy-beta-D-glucopyranoside (O-GlcNAc)
  • Spy1600
  • beta-N-acetylglucosaminidase (GlcNAcase)
  • mammalian glycoproteins
  • substrate-assisted catalysis
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Identity

PubMed Central ID

  • PMC1609908

International Standard Serial Number (ISSN)

  • 0264-6021

Digital Object Identifier (DOI)

  • 10.1042/bj20060307

PubMed ID

  • 16822234
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Additional Document Info

start page

  • 241

end page

  • 247

volume

  • 399

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