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
基因
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
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
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
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
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
参考文献
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000100448 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000040314 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Janoff A, Scherer J. Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes. The Journal of Experimental Medicine. November 1968, 128 (5): 1137–55. PMC 2138566
. PMID 5303065. doi:10.1084/jem.128.5.1137.
- ^ Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR. Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. The Journal of Clinical Investigation. December 1988, 82 (6): 1963–73. PMC 442778 . PMID 3198760. doi:10.1172/JCI113816.
- ^ Baggiolini M, Schnyder J, Bretz U, Dewald B, Ruch W. Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. Ciba Foundation Symposium. Novartis Foundation Symposia. 1979, (75): 105–21. ISBN 9780470720585. PMID 399884. doi:10.1002/9780470720585.ch7.
- ^ Virca GD, Metz G, Schnebli HP. Similarities between human and rat leukocyte elastase and cathepsin G. European Journal of Biochemistry. October 1984, 144 (1): 1–9. PMID 6566611. doi:10.1111/j.1432-1033.1984.tb08423.x.
- ^ Herrmann SM, Funke-Kaiser H, Schmidt-Petersen K, Nicaud V, Gautier-Bertrand M, Evans A, Kee F, Arveiler D, Morrison C, Orzechowski HD, Elbaz A, Amarenco P, Cambien F, Paul M. Characterization of polymorphic structure of cathepsin G gene: role in cardiovascular and cerebrovascular diseases. Arteriosclerosis, Thrombosis, and Vascular Biology. September 2001, 21 (9): 1538–43. PMID 11557685. doi:10.1161/hq0901.095555 .
- ^ Salvesen G, Enghild JJ. Zymogen activation specificity and genomic structures of human neutrophil elastase and cathepsin G reveal a new branch of the chymotrypsinogen superfamily of serine proteinases. Biomedica Biochimica Acta. 1991, 50 (4–6): 665–71. PMID 1801740.
- ^ Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J. Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. April 1987, 26 (8): 2289–93. PMID 3304423. doi:10.1021/bi00382a032.
- ^ Korkmaz B, Moreau T, Gauthier F. Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions. Biochimie. February 2008, 90 (2): 227–42. PMID 18021746. doi:10.1016/j.biochi.2007.10.009.
- ^ 13.0 13.1 Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J. Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins. Journal of Immunology. June 2014, 192 (11): 5390–7. PMC 4041364 . PMID 24771851. doi:10.4049/jimmunol.1303296.
- ^ Pham CT. Neutrophil serine proteases: specific regulators of inflammation. Nature Reviews. Immunology. July 2006, 6 (7): 541–50. PMID 16799473. S2CID 111538. doi:10.1038/nri1841.
- ^ Entrez Gene: CTSG cathepsin G.
- ^ Shafer WM, Pohl J, Onunka VC, Bangalore N, Travis J. Human lysosomal cathepsin G and granzyme B share a functionally conserved broad spectrum antibacterial peptide. The Journal of Biological Chemistry. January 1991, 266 (1): 112–6. PMID 1985886. doi:10.1016/S0021-9258(18)52409-1 .
- ^ Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, Chignard M, Pidard D. Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. Journal of Immunology. January 2004, 172 (1): 540–9. PMID 14688365. doi:10.4049/jimmunol.172.1.540 .
- ^ Bank U, Ansorge S. More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control. Journal of Leukocyte Biology. February 2001, 69 (2): 197–206. PMID 11272269. S2CID 30791872. doi:10.1189/jlb.69.2.197.
- ^ Reilly CF, Tewksbury DA, Schechter NM, Travis J. Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. The Journal of Biological Chemistry. August 1982, 257 (15): 8619–22. PMID 6807977. doi:10.1016/S0021-9258(18)34171-1 .
- ^ Sambrano GR, Huang W, Faruqi T, Mahrus S, Craik C, Coughlin SR. Cathepsin G activates protease-activated receptor-4 in human platelets. The Journal of Biological Chemistry. March 2000, 275 (10): 6819–23. PMID 10702240. doi:10.1074/jbc.275.10.6819 .
- ^ Nadel JA. Role of mast cell and neutrophil proteases in airway secretion. The American Review of Respiratory Disease. September 1991, 144 (3 Pt 2): S48–51. PMID 1892327. doi:10.1164/ajrccm/144.3_pt_2.S48.
- ^ Armao D, Kornfeld M, Estrada EY, Grossetete M, Rosenberg GA. Neutral proteases and disruption of the blood-brain barrier in rat. Brain Research. September 1997, 767 (2): 259–64. PMID 9367256. S2CID 40103486. doi:10.1016/S0006-8993(97)00567-2.
- ^ Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Current Opinion in Rheumatology. May 2007, 19 (3): 289–95. PMID 17414958. S2CID 8096646. doi:10.1097/BOR.0b013e32805e87ae.
- ^ Takei T, Sakai S, Yokonuma T, Ijima H, Kawakami K. Fabrication of artificial endothelialized tubes with predetermined three-dimensional configuration from flexible cell-enclosing alginate fibers. Biotechnology Progress. Jan–Feb 2007, 23 (1): 182–6. PMID 17269686. S2CID 40332839. doi:10.1021/bp060152j.
- ^ Liu R, Chen L, Wu W, Chen H, Zhang S. Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients. Anatolian Journal of Cardiology. January 2016, 16 (1): 23–8. PMC 5336701 . PMID 26467359. doi:10.5152/akd.2015.6072.
- ^ Komine K, Kuroishi T, Ozawa A, Komine Y, Minami T, Shimauchi H, Sugawara S. Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients. Molecular Immunology. March 2007, 44 (7): 1498–508. PMID 17030385. doi:10.1016/j.molimm.2006.09.003.
- ^ Shimoda N, Fukazawa N, Nonomura K, Fairchild RL. Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys. The American Journal of Pathology. March 2007, 170 (3): 930–40. PMC 1864870 . PMID 17322378. doi:10.2353/ajpath.2007.060486.
- ^ Kawabata K, Hagio T, Matsuoka S. The role of neutrophil elastase in acute lung injury. European Journal of Pharmacology. September 2002, 451 (1): 1–10. PMID 12223222. doi:10.1016/s0014-2999(02)02182-9.
- ^ Moraes TJ, Chow CW, Downey GP. Proteases and lung injury. Critical Care Medicine. April 2003, 31 (4 Suppl): S189–94. PMID 12682439. S2CID 45296600. doi:10.1097/01.CCM.0000057842.90746.1E.
- ^ Twigg MS, Brockbank S, Lowry P, FitzGerald SP, Taggart C, Weldon S. The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung. Mediators of Inflammation. 2015, 2015: 293053. PMC 4491392 . PMID 26185359. doi:10.1155/2015/293053 .
- ^ Liu X, Tian Y, Meng Z, Chen Y, Ho IH, Choy KW, Lichtner P, Wong SH, Yu J, Gin T, Wu WK, Cheng CH, Chan MT. Up-regulation of Cathepsin G in the Development of Chronic Postsurgical Pain: An Experimental and Clinical Genetic Study. Anesthesiology. October 2015, 123 (4): 838–50. PMID 26270939. S2CID 43571196. doi:10.1097/ALN.0000000000000828.
- ^ Whitelock RB, Fukuchi T, Zhou L, Twining SS, Sugar J, Feder RS, Yue BY. Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas. Investigative Ophthalmology & Visual Science. February 1997, 38 (2): 529–34. PMID 9040486.
- ^ Baumann M, Pham CT, Benarafa C. SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G. Blood. May 2013, 121 (19): 3900–7, S1–6. PMC 3650706 . PMID 23532733. doi:10.1182/blood-2012-09-455022.
- ^ Son ED, Shim JH, Choi H, Kim H, Lim KM, Chung JH, Byun SY, Lee TR. Cathepsin G inhibitor prevents ultraviolet B-induced photoaging in hairless mice via inhibition of fibronectin fragmentation. Dermatology. 2012, 224 (4): 352–60. PMID 22759782. S2CID 29489606. doi:10.1159/000339337.
- ^ Cruz-Silva I, Neuhof C, Gozzo AJ, Nunes VA, Hirata IY, Sampaio MU, Figueiredo-Ribeiro Rde C, Neuhof H, Araújo Mda S. Using a Caesalpinia echinata Lam. protease inhibitor as a tool for studying the roles of neutrophil elastase, cathepsin G and proteinase 3 in pulmonary edema. Phytochemistry. December 2013, 96: 235–43. PMID 24140156. doi:10.1016/j.phytochem.2013.09.025.
- ^ Craciun I, Fenner AM, Kerns RJ. N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3. Glycobiology. February 2016, 26 (7): 701–9. PMC 4976519 . PMID 26850997. doi:10.1093/glycob/cww011.
- ^ Wang J, Sjöberg S, Tang TT, Oörni K, Wu W, Liu C, Secco B, Tia V, Sukhova GK, Fernandes C, Lesner A, Kovanen PT, Libby P, Cheng X, Shi GP. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. November 2014, 1842 (11): 2174–83. PMC 4188792 . PMID 25092171. doi:10.1016/j.bbadis.2014.07.026.
拓展阅读
- Shafer WM, Katzif S, Bowers S, Fallon M, Hubalek M, Reed MS, Veprek P, Pohl J. Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens. Current Pharmaceutical Design. 2002, 8 (9): 695–702. PMID 11945165. doi:10.2174/1381612023395376.
- Cohen AB, Stevens MD, Miller EJ, Atkinson MA, Mullenbach G. Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G-treated human platelets. The American Journal of Physiology. August 1992, 263 (2 Pt 1): L249–56. PMID 1387511. doi:10.1152/ajplung.1992.263.2.L249.
- Sasaki T, Ueno-Matsuda E. Immunocytochemical localization of cathepsins B and G in odontoclasts of human deciduous teeth. Journal of Dental Research. December 1992, 71 (12): 1881–4. PMID 1452887. S2CID 27658837. doi:10.1177/00220345920710120501.
- Maison CM, Villiers CL, Colomb MG. Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G. Journal of Immunology. August 1991, 147 (3): 921–6. PMID 1861080.
- Brandt E, Van Damme J, Flad HD. Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III. Cytokine. July 1991, 3 (4): 311–21. PMID 1873479. doi:10.1016/1043-4666(91)90499-4.
- Kargi HA, Campbell EJ, Kuhn C. Elastase and cathepsin G of human monocytes: heterogeneity and subcellular localization to peroxidase-positive granules. The Journal of Histochemistry and Cytochemistry. August 1990, 38 (8): 1179–86. PMID 2164060. doi:10.1177/38.8.2164060 .
- Pratt CW, Tobin RB, Church FC. Interaction of heparin cofactor II with neutrophil elastase and cathepsin G. The Journal of Biological Chemistry. April 1990, 265 (11): 6092–7. PMID 2318847. doi:10.1016/S0021-9258(19)39296-8 .
- Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF. Antibiotic proteins of human polymorphonuclear leukocytes. Proceedings of the National Academy of Sciences of the United States of America. July 1989, 86 (14): 5610–4. Bibcode:1989PNAS...86.5610G. PMC 297672 . PMID 2501794. doi:10.1073/pnas.86.14.5610 .
- Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ. Genomic organization and chromosomal localization of the human cathepsin G gene. The Journal of Biological Chemistry. August 1989, 264 (23): 13412–9. PMID 2569462. doi:10.1016/S0021-9258(18)80012-6 .
- Livesey SA, Buescher ES, Krannig GL, Harrison DS, Linner JG, Chiovetti R. Human neutrophil granule heterogeneity: immunolocalization studies using cryofixed, dried and embedded specimens. Scanning Microscopy. Supplement. 1989, 3: 231–9; discussion 239–40. PMID 2616953.
- Campbell EJ, Silverman EK, Campbell MA. Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity. Journal of Immunology. November 1989, 143 (9): 2961–8. PMID 2681419.
- Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J. Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. April 1987, 26 (8): 2289–93. PMID 3304423. doi:10.1021/bi00382a032.
- Heck LW, Rostand KS, Hunter FA, Bhown A. Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil cathepsin G from normal donors. Analytical Biochemistry. October 1986, 158 (1): 217–27. PMID 3799965. doi:10.1016/0003-2697(86)90612-3.
- Crocker J, Jenkins R, Burnett D. Immunohistochemical localization of cathepsin G in human tissues. The American Journal of Surgical Pathology. May 1985, 9 (5): 338–43. PMID 3911778. S2CID 23124253. doi:10.1097/00000478-198505000-00003.
- Klickstein LB, Kaempfer CE, Wintroub BU. The granulocyte-angiotensin system. Angiotensin I-converting activity of cathepsin G. The Journal of Biological Chemistry. December 1982, 257 (24): 15042–6. PMID 6294088. doi:10.1016/S0021-9258(18)33390-8 .
- LaRosa CA, Rohrer MJ, Benoit SE, Barnard MR, Michelson AD. Neutrophil cathepsin G modulates the platelet surface expression of the glycoprotein (GP) Ib-IX complex by proteolysis of the von Willebrand factor binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of the remainder of the complex. Blood. July 1994, 84 (1): 158–68. PMID 7517206. doi:10.1182/blood.V84.1.158.158 .
- Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. The Journal of Cell Biology. November 1995, 131 (3): 775–89. PMC 2120617 . PMID 7593196. doi:10.1083/jcb.131.3.775.
- Savage MJ, Iqbal M, Loh T, Trusko SP, Scott R, Siman R. Cathepsin G: localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein. Neuroscience. June 1994, 60 (3): 607–19. PMID 7936190. S2CID 24998185. doi:10.1016/0306-4522(94)90490-1.
- Grisolano JL, Sclar GM, Ley TJ. Early myeloid cell-specific expression of the human cathepsin G gene in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America. September 1994, 91 (19): 8989–93. Bibcode:1994PNAS...91.8989G. PMC 44732 . PMID 8090757. doi:10.1073/pnas.91.19.8989 .
- Maruyama K, Sugano S. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene. January 1994, 138 (1–2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8.
