組織蛋白酶G
組織蛋白酶G（英文：Cathepsin G）是一種在人體中由CTSG基因編碼的蛋白質。它是儲存在嗜天青顆粒細胞中的糜蛋白酶家族的三種絲氨酸蛋白酶之一，也是肽酶S1蛋白家族的成員。組織蛋白酶G在消除細胞內病原體和分解炎症部位的組織以及抗炎反應中起重要作用。[5][6][7][8]
結構
[編輯]基因
[編輯]CTSG基因位於14號染色體q11.2，由5個外顯子組成。催化三聯體的每個殘基都位於一個單獨的外顯子上。通過掃描整個編碼區已鑑定出五個基因多態性。[9]組織蛋白酶G是通過基因複製從共同祖先進化而來的同源蛋白酶之一。[10]
蛋白質
[編輯]組織蛋白酶G是一種255-氨基酸殘基的蛋白質，包括一個18-殘基信號肽、一個N端的兩個殘基活化肽和一個C端延伸。[11]組織蛋白酶G的活性依賴於由天冬氨酸、組氨酸和絲氨酸殘基組成的催化三聯體，這些殘基在一級序列中廣泛分離，但在三級結構中酶的活性位點彼此靠近。[12]
作用
[編輯]組織蛋白酶G具有與胰凝乳蛋白酶C相似的特異性，但它與其他免疫絲氨酸蛋白酶如中性粒細胞彈性蛋白酶和顆粒酶的關係最為密切。[13]作為一種中性粒細胞絲氨酸蛋白酶，它首先被鑑定為降解酶，它在細胞內作用以降解攝入的宿主病原體，並在細胞外作用於炎症部位的細胞外基質成分的分解。[14]它定位於中性粒細胞胞外陷阱，通過其對DNA的高親和力，這是絲氨酸蛋白酶的不尋常特性。[13]該基因存在利用替代多腺苷酸化信號的轉錄變體。[15]還發現組織蛋白酶G對革蘭氏陰性菌和革蘭氏陽性菌具有廣譜抗菌作用，與上述功能無關。[16]組織蛋白酶G的其他功能已發現，包括切割受體、將血管緊張素I轉化為血管緊張素II、血小板激活和誘導氣道黏膜下腺分泌.[17][18][19][20][21]還發現了該酶在 血腦屏障 破壞中的潛在影響。[22]
臨床意義
[編輯]發現組織蛋白酶G在多種疾病中發揮重要作用，包括類風濕性關節炎、冠狀動脈疾病、牙周炎、缺血再灌注損傷和骨轉移。[23][24][25][26][27]它還與多種感染性炎症疾病有關，包括慢性阻塞性肺病、急性呼吸窘迫綜合徵和囊腫性纖維化。[28][29][30]最近的一項研究表明，具有CTSG基因多態性的患者患慢性術後疼痛的風險更高，這表明組織蛋白酶G可能作為疼痛控制的新靶點和預測慢性術後疼痛的潛在標誌物。[31]在圓錐角膜的研究中報告了組織蛋白酶G的上調。[32]
交互作用
[編輯]已發現組織蛋白酶G與以下物質相互作用：
組織蛋白酶G受以下因素抑制：
- [2-[3-[[(1-苯甲酰基-4-哌啶基)甲氨基]羰基]-2-萘基]-1-(1-萘基)-2-氧代乙基]-膦酸(KPA)[34]
- Paubrasilia彈性蛋白酶抑制劑[35]
- N-芳酰基O-磺化氨基糖苷類[36]
組織蛋白酶G降低以下水平：
參見
[編輯]參考文獻
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拓展閱讀
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