Biochemistry & Microbiology, University of Victoria, Victoria, BC, Canada.
Structure. 2011 May 11;19(5):640-51. doi: 10.1016/j.str.2011.03.001.
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.
SpuA 是一种大型的多模块细胞壁附着酶，参与致病性肺炎链球菌对糖原的降解。从细菌中删除编码 SpuA 的基因导致与亲本菌株相比，在毒性的小鼠模型中竞争力降低的菌株，将宿主糖原的降解与细菌的毒性联系起来。通过 X 射线晶体学、小角度 X 射线散射和抑制剂结合的综合使用，揭示了涉及该复合蛋白底物识别的分子特征。这独特地说明了活性位点的复杂性、该蛋白在碳水化合物结合过程中发生的构象变化，以及在这个过程中其复合模块的相互作用和协作。为理解多模块碳水化合物活性酶中模块之间的结构和功能相互作用提供了新的见解，同时为理解这一特定肺炎球菌毒力因子的功能提供了实质性的贡献。
