组织蛋白酶G
组织蛋白酶G（英文：Cathepsin G）是一种在人体中由CTSG基因编码的蛋白质。它是储存在嗜天青颗粒细胞中的糜蛋白酶家族的三种丝氨酸蛋白酶之一，也是肽酶S1蛋白家族的成员。组织蛋白酶G在消除细胞内病原体和分解炎症部位的组织以及抗炎反应中起重要作用。[5][6][7][8]
结构
[编辑]基因
[编辑]CTSG基因位于14号染色体q11.2，由5个外显子组成。催化三联体的每个残基都位于一个单独的外显子上。通过扫描整个编码区已鉴定出五个基因多态性。[9]组织蛋白酶G是通过基因复制从共同祖先进化而来的同源蛋白酶之一。[10]
蛋白质
[编辑]组织蛋白酶G是一种255-氨基酸残基的蛋白质，包括一个18-残基信号肽、一个N端的两个残基活化肽和一个C端延伸。[11]组织蛋白酶G的活性依赖于由天冬氨酸、组氨酸和丝氨酸残基组成的催化三联体，这些残基在一级序列中广泛分离，但在三级结构中酶的活性位点彼此靠近。[12]
作用
[编辑]组织蛋白酶G具有与胰凝乳蛋白酶C相似的特异性，但它与其他免疫丝氨酸蛋白酶如中性粒细胞弹性蛋白酶和颗粒酶的关系最为密切。[13]作为一种中性粒细胞丝氨酸蛋白酶，它首先被鉴定为降解酶，它在细胞内作用以降解摄入的宿主病原体，并在细胞外作用于炎症部位的细胞外基质成分的分解。[14]它定位于中性粒细胞胞外陷阱，通过其对DNA的高亲和力，这是丝氨酸蛋白酶的不寻常特性。[13]该基因存在利用替代多腺苷酸化信号的转录变体。[15]还发现组织蛋白酶G对革兰氏阴性菌和革兰氏阳性菌具有广谱抗菌作用，与上述功能无关。[16]组织蛋白酶G的其他功能已发现，包括切割受体、将血管紧张素I转化为血管紧张素II、血小板激活和诱导气道黏膜下腺分泌.[17][18][19][20][21]还发现了该酶在 血脑屏障 破坏中的潜在影响。[22]
临床意义
[编辑]发现组织蛋白酶G在多种疾病中发挥重要作用，包括类风湿性关节炎、冠状动脉疾病、牙周炎、缺血再灌注损伤和骨转移。[23][24][25][26][27]它还与多种感染性炎症疾病有关，包括慢性阻塞性肺病、急性呼吸窘迫综合征和囊腫性纖維化。[28][29][30]最近的一项研究表明，具有CTSG基因多态性的患者患慢性术后疼痛的风险更高，这表明组织蛋白酶G可能作为疼痛控制的新靶点和预测慢性术后疼痛的潜在标志物。[31]在圆锥角膜的研究中报告了组织蛋白酶G的上调。[32]
交互作用
[编辑]已发现组织蛋白酶G与以下物质相互作用：
组织蛋白酶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弹性蛋白酶抑制剂[35]
- N-芳酰基O-磺化氨基糖苷类[36]
组织蛋白酶G降低以下水平：
参见
[编辑]参考文献
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拓展阅读
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