Therapeutic Establishment for Gingival Hyperplasia and Scar Formation by Use of Collagen-Digestible Proteases

使用胶原蛋白消化蛋白酶治疗牙龈增生和疤痕形成的治疗方法的建立

• 批准号: 21592367
• 负责人: NEMOTO Takayuki
• 金额: $ 3万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592367/
• 关键词: ブドウ球菌性熱傷様皮膚症候群; とびひ; 歯周病; Staphylococcus aureus; Porphyromonas gingivalis; ジペプチジルペプチダーゼ; 熱傷様皮膚症候群; 表皮剥脱毒素; DPP7; DPP11; ETA; 黄色ブドウ球菌; セリンプロテアーゼ; グルタミン酸特異的; リコンビナント体; コラーゲン; グルタミン酸特異的プロテアーゼ; コアグラーゼ ポジティブ; プロセシング; ブドウ球菌性熱傷様皮膚症候群; とびひ; 歯周病; Staphylococcus aureus; Porphyromonas gingivalis; ジペプチジルペプチダーゼ; 熱傷様皮膚症候群; 表皮剥脱毒素; DPP7; DPP11; ETA; 黄色ブドウ球菌; セリンプロテアーゼ; グルタミン酸特異的; リコンビナント体; コラーゲン; グルタミン酸特異的プロテアーゼ; コアグラーゼ ポジティブ; プロセシング

Porphyromonas gingivalis and Porphyromonas endodontalis, asaccharolytic black-pigmented anaerobes, are predominant pathogens of human chronic and periapical periodontitis, respectively. They incorporate di-and tri-peptides from the environment as carbon and energy sources. In the present study, we cloned a novel dipeptidyl peptidase(DPP) gene of P. endodontalis ATCC 35406, designated as DPP11. A homology search revealed the presence of a P. gingivalis orthologue, PGN0607, which has been categorized as an isoform of authentic DPP7. DPP11 specifically removed dipeptides from oligopeptides with the penultimate N-terminal Asp and Glu. Arg_<670> is a unique amino acid completely conserved in all DPP11 members, whilst this residue is converted to Gly in all authentic DPP7 members. Substitution analysis suggested that Arg_<670> interacts with an acidic residue of the substrate. Considered to preferentially utilize acidic amino acids, DPP11 ensures efficient degradation of oligopeptide substrates in these gram-negative anaerobic rods.In order to investigate the mechanism of Staphylococcal scalded skin syndrome(SSSS) caused by exfoliative toxin A(ETA), we expressed and purified ETA and its N-terminally truncated(Δ38 andΔ57) and inactive(Ser233Ala) derivatives in E. coli. Recombinant ETA(wt) showed the peptidase activity for LLE-MCA. This is the first report that ETA showed the peptidase activity other than Dsg1. ETA and its dirivatives exerted toxin activity to newborn mice, if ETA derivatives(wt andΔ38) possessed the peptidase activity, while ETAs with no peptidase activity(Δ57 and SerΔ233Ala) did not cause the disease. This finding indicated that the peptidase activity of ETA was indispensible for the toxin activity.

卟啉单胞菌和卟啉单胞菌，酶散发性黑色色素的厌氧菌分别是人类慢性和周围牙周炎的主要病原体。他们将来自环境的DI-di和三肽作为碳和能源纳入。在介绍研究中，我们克隆了一个新型的dp. hendodontalis atcc 35406的新型二肽基肽（DPP）基因，该基因设计为DPP11。同源性搜索揭示了牙龈疟原虫直系同源物PGN0607的存在，该物质已被归类为真实DPP7的同工型。 DPP11通过倒数第二个末端ASP和GLU从寡肽中特异性去除二肽。 Arg_ <670>是在所有DPP11成员中完全保守的独特氨基酸，而该住宅在所有真实的DPP7成员中都转化为Gly。替代分析表明，arg_ <670>与底物的酸性残基相互作用。 DPP11被认为优先利用酸性氨基酸，确保在这些革兰氏阴性厌氧棒中有效地降解寡肽底物。为了研究葡萄球菌烫伤的皮肤综合征（SSS）的机制AndΔ57）和大肠杆菌中的非活性（SER233ALA）衍生物。重组ETA（WT）显示LLE-MCA的肽酶活性。这是ETA表现出除DSG1以外的肽酶活动的第一个报告。如果Eta衍生物（WT和Δ38）具有肽蛋白活性，而ETA及其远向剂对新生小鼠进行了毒素活性，而没有肽酶活性的ETA（Δ57和SerΔ2333Ala）并未引起疾病。这一发现表明，ETA的肽酶活性对于毒素活性是不可或缺的。