Crystal structures of the GH18 domain of the bifunctional peroxiredoxin-chitinase CotE from Clostridium difficile.
Crystal structures of the GH18 domain of the bifunctional peroxiredoxin-chitinase CotE from Clostridium difficile.
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来自艰难梭菌的双功能过氧化还原蛋白-几丁质酶 CotE 的 GH18 结构域的晶体结构。
DOI：
10.1107/s2053230x20006147
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Whittingham JL
中科院分区：
文献类型：
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作者：
Whittingham JL
CotE是一种存在于艰难梭菌孢子中的外壳蛋白，艰难梭菌是一种专性厌氧菌，也是医院患者腹泻相关性腹泻的主要原因。孢子作为疾病传播的媒介，CotE与它们对肠道上皮的附着和随后的宿主定殖有关。CotE由N-末端过氧化物氧还蛋白结构域和C-末端几丁质酶结构域组成。在此，包含残基349-712的CotE的C-末端片段已经结晶，并且其结构已经被确定为揭示核心八链β-桶折叠，其中相邻的亚结构域包含五链β-折叠。一个突出的凹槽贯穿桶的顶部，由家族18糖基水解酶中保守的残基排列，并参与催化。在沟槽中鉴定的电子密度定义了在蛋白水解切割以去除亲和纯化标签后衍生自蛋白质N-末端的五肽Gly-Pro-Ala-Met-Lys。这些观察结果表明设计肽模拟物来阻断C的可能性。艰难的传输。
CotE is a coat protein that is present in the spores of Clostridium difficile, an obligate anaerobic bacterium and a pathogen that is a leading cause of antibiotic-associated diarrhoea in hospital patients. Spores serve as the agents of disease transmission, and CotE has been implicated in their attachment to the gut epithelium and subsequent colonization of the host. CotE consists of an N-terminal peroxiredoxin domain and a C-terminal chitinase domain. Here, a C-terminal fragment of CotE comprising residues 349–712 has been crystallized and its structure has been determined to reveal a core eight-stranded β-barrel fold with a neighbouring subdomain containing a five-stranded β-sheet. A prominent groove running across the top of the barrel is lined by residues that are conserved in family 18 glycosyl hydrolases and which participate in catalysis. Electron density identified in the groove defines the pentapeptide Gly-Pro-Ala-Met-Lys derived from the N-terminus of the protein following proteolytic cleavage to remove an affinity-purification tag. These observations suggest the possibility of designing peptidomimetics to block C. difficile transmission.