The Conformation and Function of a Multimodular Glycogen-Degrading Pneumococcal Virulence Factor

Alicia Lammerts van Bueren, Elizabeth Ficko-Blean, Benjamin Pluvinage, Jan-Hendrik Hehemann, Melanie Higgins, Lehua Deng, David Ogunniyi, Uwe Stroeher, Nahida El Warry, Robert Burke, Mirjam Czjzek, James Paton, David Vocadlo, Alisdair Boraston

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)640-651
    Number of pages12
    JournalSTRUCTURE
    Volume19
    Issue number5
    DOIs
    Publication statusPublished - 2011

    Fingerprint Dive into the research topics of 'The Conformation and Function of a Multimodular Glycogen-Degrading Pneumococcal Virulence Factor'. Together they form a unique fingerprint.

  • Cite this

    Lammerts van Bueren, A., Ficko-Blean, E., Pluvinage, B., Hehemann, J-H., Higgins, M., Deng, L., Ogunniyi, D., Stroeher, U., El Warry, N., Burke, R., Czjzek, M., Paton, J., Vocadlo, D., & Boraston, A. (2011). The Conformation and Function of a Multimodular Glycogen-Degrading Pneumococcal Virulence Factor. STRUCTURE, 19(5), 640-651. https://doi.org/10.1016/j.str.2011.03.001