Successful pathogenesis is a cumulative effect of the virulence factors of a pathogen and its capability to efficiently utilize the available nutrients from the host. Streptococcus pneumoniae, a Gram‐positive opportunistic pathogen, may either reside asymptomatically as a nasopharyngeal commensal inside the human host or cause lethal diseases, including pneumonia, meningitis and sepsis. S. pneumoniae is known to acquire methionine (Met) from its host through a Met importer. Here, the crystal structure of the substrate‐binding protein (SBP; SP_0149) of an ABC importer with Met bound is reported at a resolution of 1.95 Å. The three‐dimensional structure of SBP shows that it is composed of two distinct domains, each consisting of a mixed β‐sheet flanked by helices. The substrate, Met, is bound in the central part of the interface between the two domains. The overall structure of SP_0149 resembles those of SBPs from other reported bacterial Met and Gly‐Met dipeptide transporters. However, a detailed analysis of these structures shows notable variations in the amino‐acid composition of the substrate‐binding pockets of the SP_0149–Met and GmpC–Gly‐Met structures. In particular, SP_0149 harbors Thr212 and Tyr114, whereas the corresponding residues in GmpC are Gly and Val. This difference is likely to be the underlying basis for their differential substrate specificity. In summary, the structure of the SP_0149–Met complex provides insights into the transport function of SP_0149 and its interactions with methionine. It opens up avenues for the rational design of inhibitors of SP_0149 through a structure‐mediated approach.

中文翻译：

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对 SP_0149 底物特异性的结构见解，SP_0149 是肺炎链球菌甲硫氨酸 ABC 转运蛋白的底物结合蛋白。


成功的发病机制是病原体毒力因子的累积效应及其有效利用宿主可用营养物质的能力。肺炎链球菌是一种革兰氏阳性机会致病菌，可能作为鼻咽共生菌无症状地存在于人体内，也可能引起致命疾病，包括肺炎、脑膜炎和败血症。已知肺炎链球菌通过 Met 进口商从其宿主获取蛋氨酸 (Met)。此处，报告了结合 Met 的 ABC 输入蛋白的底物结合蛋白 (SBP；SP_0149) 的晶体结构，分辨率为 1.95 Å。 SBP 的三维结构表明它由两个不同的结构域组成，每个结构域均由侧翼为螺旋的混合 β 折叠组成。底物 Met 结合在两个域之间界面的中心部分。 SP_0149 的整体结构类似于其他报道的细菌 Met 和 Gly-Met 二肽转运蛋白的 SBP。然而，对这些结构的详细分析显示 SP_0149-Met 和 GmpC-Gly-Met 结构的底物结合袋的氨基酸组成存在显着变化。特别是，SP_0149 含有 Thr212 和 Tyr114，而 GmpC 中相应的残基是 Gly 和 Val。这种差异可能是其底物特异性差异的根本基础。总之，SP_0149-Met 复合物的结构提供了对 SP_0149 转运功能及其与蛋氨酸相互作用的见解。它为通过结构介导的方法合理设计 SP_0149 抑制剂开辟了途径。