Książek Mirosław, Goulas Theodoros, Mizgalska Danuta, Rodríguez-Banqueri Arturo, Eckhard Ulrich, Veillard Florian, Waligórska Irena, Benedyk-Machaczka Małgorzata, Sochaj-Gregorczyk Alicja M, Madej Mariusz, Thøgersen Ida B, Enghild Jan J, Cuppari Anna, Arolas Joan L, de Diego Iñaki, López-Pelegrín Mar, Garcia-Ferrer Irene, Guevara Tibisay, Dive Vincent, Zani Marie-Louise, Moreau Thierry, Potempa Jan, Gomis-Rüth F Xavier
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University Gronostajowa 7 Kraków 30-387 Poland
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry Louisville 40202 KY USA.
Chem Sci. 2022 Dec 12;14(4):869-888. doi: 10.1039/d2sc04166a. eCollection 2023 Jan 25.
Periodontopathogenic uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98-132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of , as shown . Remarkably, PotA also contributes to bacterial fitness and specifically inhibits matrix metallopeptidase (MMP) 12, a major defence component of oral macrophages, thus featuring a novel and highly-specific physiological MMP inhibitor. Information from 11 structures and high-confidence homology models showed that the potempins are distinct β-barrels with either a five-stranded OB-fold (PotA, PotC and PotD) or an eight-stranded up-and-down fold (PotE, PotB1 and PotB2), which are novel for peptidase inhibitors. Particular loops insert like wedges into the active-site cleft of the genetically-linked peptidases to specifically block them either a new "bilobal" or the classic "standard" mechanism of inhibition. These results discover a unique, tightly-regulated proteolytic armamentarium for virulence and competence, the KLIKK-peptidase/potempin system.
牙周致病菌独特地分泌六种催化类别和家族不同的肽酶，即KLIKK肽酶，它们在牙龈感染期间作为毒力因子发挥作用。它们的编码基因紧挨着编码98 - 132个残基的Potempins（Pot）A、B1、B2、C、D和E的新开放阅读框下游。这些是外膜锚定脂蛋白，通过稳定的复合物特异性且有效地抑制各自下游的肽酶，如所示保护……的外膜。值得注意的是，PotA还对细菌适应性有贡献，并特异性抑制口腔巨噬细胞的主要防御成分基质金属肽酶（MMP）12，从而成为一种新型且高度特异性的生理性MMP抑制剂。来自11个结构和高可信度同源模型的信息表明，Potempins是独特的β桶结构，要么具有五链OB折叠（PotA、PotC和PotD），要么具有八链上下折叠（PotE、PotB1和PotB2），这对于肽酶抑制剂来说是新颖的。特定的环像楔子一样插入到基因相连的肽酶的活性位点裂隙中，以新的“双叶”或经典的“标准”抑制机制特异性地阻断它们。这些结果发现了一种独特的、严格调控的用于毒力和能力的蛋白水解武器库，即KLIKK肽酶/Potempin系统。
