title: The conformation and function of a multimodular glycogen-degrading pneumococcal virulence factor.
abstract: SpuA is a large multimodular cell wall-attached enzyme involved in the degradation of glycogen by the pathogenic bacterium Streptococcus pneumoniae. The deletion of the gene encoding SpuA from the bacterium resulted in a strain with reduced competitiveness in a mouse model of virulence relative to the parent strain, linking the degradation of host-glycogen to the virulence of the bacterium. Through the combined use of X-ray crystallography, small-angle X-ray scattering, and inhibitor binding, the molecular features involved in substrate recognition by this complex protein are revealed. This uniquely illustrates the complexity of the active site, the conformational changes incurred during carbohydrate binding by this protein, and the interaction and cooperation of its composite modules during this process. New insight into the function of this particular pneumococcal virulence factor is provided along with substantial contributions to the nascent framework for understanding the structural and functional interplay between modules in multimodular carbohydrate-active enzymes.
authors.affiliation: Biochemistry & Microbiology, University of Victoria, Victoria, BC, Canada.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lammerts van Bueren
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ficko-Blean
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pluvinage
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Hehemann
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Higgins
authors.forename: Lehua
authors.initials: L
authors.lastname: Deng
authors.forename: A David
authors.initials: AD
authors.lastname: Ogunniyi
authors.forename: Uwe H
authors.initials: UH
authors.lastname: Stroeher
authors.forename: Nahida
authors.initials: N
authors.lastname: El Warry
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burke
authors.forename: Mirjam
authors.initials: M
authors.lastname: Czjzek
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: David J
authors.initials: DJ
authors.lastname: Vocadlo
authors.forename: Alisdair B
authors.initials: AB
authors.lastname: Boraston
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006003:Glycogen / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000473:pathology; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D037521:Virulence Factors; D006003:Glycogen; D006026:Glycoside Hydrolases