Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage.
Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage.
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DOI：
10.1515/bc.2009.136
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发表时间：
2009-12
影响因子：
3.7
通讯作者：
Meyer-Hoffert U
中科院分区：
文献类型：
--
作者：
Kantyka T;Latendorf T;Wiedow O;Bartels J;Gläser R;Dubin G;Schröder JM;Potempa J;Meyer-Hoffert U
牙龈卟啉单胞菌（Porphyromonas gingivalis）是牙周炎的主要致病菌，由于细菌和宿主（主要是嗜酸性粒细胞来源的）丝氨酸蛋白酶的存在，其显著地有助于牙周袋处蛋白水解活性的升高。通常，后一种酶的活性受到内源性蛋白质的严格调节，所述内源性蛋白质包括弹性蛋白酶（elafin），一种从炎症部位的上皮细胞释放的有效的中性粒细胞弹性蛋白酶和蛋白酶3抑制剂。在这里，我们发现所有三种牙龈卟啉菌蛋白酶（HRgpA、RgpB和Kgp）都能够降解弹性蛋白酶，但RgpB比其他牙龈卟啉菌蛋白酶更有效。RgpB已经通过限制于包含抑制剂活性位点的表面环内的Arg 22-Cys 23肽键的蛋白水解有效地灭活了亚纳摩尔浓度的弹性蛋白酶的抑制活性。值得注意的是，弹性蛋白抵抗几种金黄色葡萄球菌来源的丝氨酸和半胱氨酸蛋白酶的失活，证实了这种蛋白质对蛋白水解降解的高稳定性。因此，我们得出结论，弹性蛋白RgpB失活代表了牙龈卟啉单胞菌的一种特异性致病适应，以干扰感染牙龈组织中的蛋白酶-蛋白酶抑制剂平衡。这有助于增强宿主蛋白质的降解和产生作为这种溶砷病原体的营养物的肽库。
Porphyromonas gingivalis, the major causative bacterium of periodontitis, contributes significantly to elevated proteolytic activity at periodontal pockets due to the presence of both, bacteria and host, predominantly neutrophil-derived, serine proteases. Normally the activity of the latter enzymes is tightly regulated by endogenous proteins, including elafin, a potent neutrophil elastase and proteinase 3 inhibitor released from epithelial cells at site of inflammation. Here we have found that all three gingipains (HRgpA, RgpB and Kgp) were able to degrade elafin but RgpB was far more efficient than other gingipains. RgpB already inactivated efficiently the inhibitory activity of elafin at subnanomolar concentrations through a proteolysis limited to the Arg22-Cys23 peptide bond within the surface loop harbouring the inhibitor active site. Notably, elafin resisted inactivation by several Staphylococcus aureus-derived serine- and cysteine proteases confirming this protein's high stability for proteolytic degradation. Therefore, we concluded that elafin inactivation by RgpB represents a specific pathogenic adaptation of P. gingivalis to disturb the protease-protease inhibitor balance in the infected gingival tissue. This contributes to enhanced degradation of host proteins and generation of a pool of peptides serving as nutrients for this asaccharolytic pathogen.