5NCU

Structure of the subtilisin induced serpin-type proteinase inhibitor, miropin.

5NCU の概要

• エントリーDOI: 10.2210/pdb5ncu/pdb
• 関連するPDBエントリー: 5NCS
• 分子名称: Serpin, POTASSIUM ION, IODIDE ION, ... (7 entities in total)
• 機能のキーワード: serpin-type proteinase inhibitor, hydrolase inhibitor
• 由来する生物種: Tannerella forsythia; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43218.39

構造登録者

Goulas, T.,Ksiazek, M.,Garcia-Ferrer, I.,Mizgalska, D.,Potempa, J.,Gomis-Ruth, X. (登録日: 2017-03-06, 公開日: 2017-05-24, 最終更新日: 2024-01-17)

主引用文献

Goulas, T.,Ksiazek, M.,Garcia-Ferrer, I.,Sochaj-Gregorczyk, A.M.,Waligorska, I.,Wasylewski, M.,Potempa, J.,Gomis-Ruth, F.X.
A structure-derived snap-trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome.
J. Biol. Chem., 292:10883-10898, 2017

PubMed Abstract: Enduring host-microbiome relationships are based on adaptive strategies within a particular ecological niche. is a dysbiotic member of the human oral microbiome that inhabits periodontal pockets and contributes to chronic periodontitis. To counteract endopeptidases from the host or microbial competitors, possesses a serpin-type proteinase inhibitor called miropin. Although serpins from animals, plants, and viruses have been widely studied, those from prokaryotes have received only limited attention. Here we show that miropin uses the serpin-type suicidal mechanism. We found that, similar to a snap trap, the protein transits from a metastable native form to a relaxed triggered or induced form after cleavage of a reactive-site target bond in an exposed reactive-center loop. The prey peptidase becomes covalently attached to the inhibitor, is dragged 75 Å apart, and is irreversibly inhibited. This coincides with a large conformational rearrangement of miropin, which inserts the segment upstream of the cleavage site as an extra β-strand in a central β-sheet. Standard serpins possess a single target bond and inhibit selected endopeptidases of particular specificity and class. In contrast, miropin uniquely blocked many serine and cysteine endopeptidases of disparate architecture and substrate specificity owing to several potential target bonds within the reactive-center loop and to plasticity in accommodating extra β-strands of variable length. Phylogenetic studies revealed a patchy distribution of bacterial serpins incompatible with a vertical descent model. This finding suggests that miropin was acquired from the host through horizontal gene transfer, perhaps facilitated by the long and intimate association of with the human gingiva.

PubMed: 28512127
DOI: 10.1074/jbc.M117.786533

実験手法

X-RAY DIFFRACTION (1.7 Å)