Crystal structure of a hypothetical protein from Giardia lamblia.
Crystal structure of a hypothetical protein from Giardia lamblia.
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DOI：
10.1107/s2053230x21013595
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发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Asojo OA
中科院分区：
文献类型：
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作者：
Beard DK;Bristol S;Cosby K;Davis A;Manning C;Perry L;Snapp L;Toy A;Wheeler K;Young J;Staker B;Arakaki TL;Abendroth J;Subrahamanian S;Edwards TE;Myler PJ;Asojo OA
作为结构基因组研究的一部分，确定了寄生虫贾第虫蓝氏贾第虫的15.6 kDa假设蛋白质的1.35μ m分辨率晶体结构，以分配可能的功能给来自感染因子的假设蛋白质。 该结构具有典型的核糖核酸内切酶L-PSP（肝高氯酸可溶性蛋白）拓扑结构，具有保守的变构活性位点残基，尽管与该超家族的其他成员缺乏任何明显的序列同一性。贾第虫病是全球最流行的肠道疾病，影响人类和动物。这是发展中国家的一个重大问题，是旅行者腹泻的头号原因，影响儿童和免疫功能低下的个体，特别是HIV感染者。贾第虫病是用抗生素（替硝唑和甲硝唑）治疗，也用于其他感染，如滴虫病。目前正在寻找新的治疗贾第鞭毛虫病的方法，包括表征病原性原生动物贾第鞭毛虫的蛋白质的结构和功能。这些蛋白质包括与已知结构的蛋白质共享30%或更少序列同一性的假设蛋白质。在这里，通过分子置换确定了15.6 kDa蛋白质的原子分辨率结构。 该结构具有在原型内切核糖核酸酶L-PSP（肝高氯酸可溶性蛋白）中观察到的双层αβ-夹心拓扑结构，具有包含来自结晶溶液的小分子的保守变构活性位点。本文是汉普顿大学和西雅图传染病结构基因组学中心之间的教育合作。
The 1.35 Å resolution crystal structure of a 15.6 kDa hypothetical protein from the parasite Giardia lamblia was determined as part of structural genomic studies to assign possible functions to hypothetical proteins from infectious agents. The structure has a prototypical endoribonuclease L-PSP (liver perchloric acid-soluble protein) topology with conserved allosteric active-site residues despite lacking any appreciable sequence identity to other members of this superfamily. Giardiasis is the most prevalent diarrheal disease globally and affects humans and animals. It is a significant problem in developing countries, the number one cause of travelers’ diarrhea and affects children and immunocompromised individuals, especially HIV-infected individuals. Giardiasis is treated with antibiotics (tinidazole and metronidazole) that are also used for other infections such as trichomoniasis. The ongoing search for new therapeutics for giardiasis includes characterizing the structure and function of proteins from the causative protozoan Giardia lamblia. These proteins include hypothetical proteins that share 30% sequence identity or less with proteins of known structure. Here, the atomic resolution structure of a 15.6 kDa protein was determined by molecular replacement. The structure has the two-layer αβ-sandwich topology observed in the prototypical endoribonucleases L-PSPs (liver perchloric acid-soluble proteins) with conserved allosteric active sites containing small molecules from the crystallization solution. This article is an educational collaboration between Hampton University and the Seattle Structural Genomics Center for Infectious Disease.