Conformational flexibility in the zinc solute-binding protein ZnuA.
Conformational flexibility in the zinc solute-binding protein ZnuA.
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锌溶质结合蛋白Znua中的构象柔韧性。
DOI：
10.1107/s2053230x22001662
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发表时间：
2022-03-01
期刊：
影响因子：
--
通讯作者：
Yukl E
中科院分区：
文献类型：
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作者：
Yekwa EL;Serrano FA;Yukl E
在细菌中，高亲和力的锌输入是通过 ATP 结合盒 (ABC) 转运蛋白完成的，该转运蛋白依赖细胞外溶质结合蛋白 (SBP) 来获取金属并将其递送至膜渗透酶。科塞柠檬酸杆菌 SBP ZnuA 的锌结合（全）形式的晶体结构已确定。尽管与肠沙门氏菌的 ZnuA 同源物有 95% 的序列同一性，但 C. koseri ZnuA 表现出不同的锌配位和封闭而非开放的构象。与其他紧密的 ZnuA 同源结构的比较表明，灵活的构象景观可能对于锌的结合和/或递送至通透酶很重要。锌是所有生命领域的必需金属，使其穿过细胞膜的运输成为一个关键功能。在细菌中，高亲和力的锌输入是通过 ATP 结合盒 (ABC) 转运蛋白完成的，该转运蛋白依赖 A-I 簇的胞外溶质结合蛋白 (SBP) 来获取金属并将其递送至膜渗透酶。这些系统对于生存和毒力很重要，使其成为新型抗生素开发的有吸引力的目标。科塞柠檬酸杆菌是一种新兴的病原体，具有广泛的抗生素耐药性。与 C. koseri 簇 A-I SBP ZnuA 结合的高亲和力锌已被表征，并且锌结合（全息）形式的结构已通过 X 射线晶体学确定。值得注意的是，尽管 C. koseri ZnuA 与肠沙门氏菌的 ZnuA 同源物有 95% 的序列同一性，但它表现出不同的锌配位环境和封闭而非开放的构象。与来自大肠杆菌的另一种接近的 ZnuA 同源物的结构进行比较表明，其具有令人惊讶的灵活构象景观，这对于锌的有效结合和/或递送至膜通透酶可能很重要。
In bacteria, high-affinity zinc import is accomplished by ATP-binding cassette (ABC) transporters, which rely on extracellular solute-binding proteins (SBPs) to acquire the metal and deliver it to the membrane permease. The crystal structure of the zinc-bound (holo) form of Citrobacter koseri SBP ZnuA has been determined. Despite 95% sequence identity to the ZnuA homologue from Salmonella enterica, C. koseri ZnuA exhibits different zinc-coordination and a closed rather than open conformation. Comparison with other close ZnuA homologue structures suggests a flexible conformational landscape that may be important for zinc binding and/or delivery to the permease. Zinc is an essential metal for all kingdoms of life, making its transport across the cell membrane a critical function. In bacteria, high-affinity zinc import is accomplished by ATP-binding cassette (ABC) transporters, which rely on extracellular solute-binding proteins (SBPs) of cluster A-I to acquire the metal and deliver it to the membrane permease. These systems are important for survival and virulence, making them attractive targets for the development of novel antibiotics. Citrobacter koseri is an emerging pathogen with extensive antibiotic resistance. High-affinity zinc binding to the C. koseri cluster A-I SBP ZnuA has been characterized and the structure of the zinc-bound (holo) form has been determined by X-ray crystallography. Remarkably, despite 95% sequence identity to the ZnuA homologue from Salmonella enterica, C. koseri ZnuA exhibits a different zinc-coordination environment and a closed rather than an open conformation. Comparison with structures of another close ZnuA homologue from Escherichia coli suggests a surprisingly flexible conformational landscape that may be important for efficient zinc binding and/or delivery to the membrane permease.