基于statine的抑制剂对多种人天冬氨酸蛋白酶的选择性。
The selectivity of statine-based inhibitors against various human aspartic proteinases.
作者信息
Jupp R A, Dunn B M, Jacobs J W, Vlasuk G, Arcuri K E, Veber D F, Perlow D S, Payne L S, Boger J, de Laszlo S
机构信息
Department of Biochemistry, University of Wales College of Cardiff, U.K.
出版信息
Biochem J. 1990 Feb 1;265(3):871-8. doi: 10.1042/bj2650871.
Abstract
The interactions of five human enzymes (renin, pepsin, gastricsin, cathepsin D and cathepsin E) and the aspartic proteinase from Endothia parasitica with several series of synthetic inhibitors were examined. All of the inhibitors contained the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues in the P1-P1' positions. The residues occupying the peripheral sub-sites (P4 to P3') were varied systematically and inhibitory constants were determined for the interactions with each of the proteinases. Inhibitors were elucidated that specifically inhibited human renin and did not affect any of the other human enzymes or the fungal proteinase. With suitable selection of residues to occupy individual sub-sites, effective inhibitors of specific human aspartic proteinases may now be designed.
摘要
研究了五种人类酶（肾素、胃蛋白酶、胃泌酶、组织蛋白酶D和组织蛋白酶E）以及寄生内座壳天冬氨酸蛋白酶与几系列合成抑制剂的相互作用。所有抑制剂在P1-P1'位置均含有二肽类似物司他汀或其苯丙氨酸或环己基丙氨酸同系物。系统地改变占据外周亚位点（P4至P3'）的残基，并测定与每种蛋白酶相互作用的抑制常数。已阐明了特异性抑制人类肾素且不影响任何其他人类酶或真菌蛋白酶的抑制剂。通过适当选择占据各个亚位点的残基，现在可以设计出特异性人类天冬氨酸蛋白酶的有效抑制剂。
相似文献
1
The selectivity of statine-based inhibitors against various human aspartic proteinases.基于statine的抑制剂对多种人天冬氨酸蛋白酶的选择性。
Biochem J. 1990 Feb 1;265(3):871-8. doi: 10.1042/bj2650871.
2
X-ray studies of aspartic proteinase-statine inhibitor complexes.天冬氨酸蛋白酶-西司他丁抑制剂复合物的X射线研究。
Biochemistry. 1989 Oct 17;28(21):8596-603. doi: 10.1021/bi00447a049.
3
Inhibition of human napsin A.
Protein Pept Lett. 2003 Feb;10(1):35-42. doi: 10.2174/0929866033408237.
4
Inhibition of porcine pepsin by two substrate analogues containing statine. The effect of histidine at the P2 subsite on the inhibition of aspartic proteinases.含沙他汀的两种底物类似物对猪胃蛋白酶的抑制作用。P2亚位点的组氨酸对天冬氨酸蛋白酶抑制作用的影响。
J Med Chem. 1988 Mar;31(3):625-9. doi: 10.1021/jm00398a022.
5
Inhibition of aspartic proteinases by synthetic peptides derived from the propart region of human prorenin.
Int J Biochem. 1992 Feb;24(2):297-301. doi: 10.1016/0020-711x(92)90261-x.
6
The pH dependence of the hydrolysis of chromogenic substrates of the type, Lys-Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu, by selected aspartic proteinases: evidence for specific interactions in subsites S3 and S2.特定天冬氨酸蛋白酶对Lys-Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu型生色底物水解的pH依赖性：S3和S2亚位点特异性相互作用的证据
Biochim Biophys Acta. 1987 Jun 17;913(2):122-30. doi: 10.1016/0167-4838(87)90320-7.
7
Comparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
Adv Exp Med Biol. 1995;362:155-66. doi: 10.1007/978-1-4615-1871-6_20.
8
Substrate specificities and kinetic properties of proteinase A from the yeast Saccharomyces cerevisiae and the development of a novel substrate.酿酒酵母蛋白酶A的底物特异性和动力学特性以及一种新型底物的开发
J Biochem. 1998 Jul;124(1):141-7. doi: 10.1093/oxfordjournals.jbchem.a022072.
9
Shewasin A, an active pepsin homolog from the bacterium Shewanella amazonensis.她来自 A 蛋白，一种来自亚马逊希瓦氏菌的活性胃蛋白酶同源物。
FEBS J. 2011 Sep;278(17):3177-86. doi: 10.1111/j.1742-4658.2011.08243.x. Epub 2011 Aug 11.
10
Substrate specificity and inhibitors of aspartic proteinases.
Scand J Clin Lab Invest Suppl. 1992;210:23-30.
引用本文的文献
1
Cathepsin D-Managing the Delicate Balance.组织蛋白酶D——维持微妙平衡
Pharmaceutics. 2021 Jun 5;13(6):837. doi: 10.3390/pharmaceutics13060837.
2
Selective detection of Cathepsin E proteolytic activity.组织蛋白酶E蛋白水解活性的选择性检测
Biochim Biophys Acta. 2010 Sep;1800(9):1002-8. doi: 10.1016/j.bbagen.2010.06.005. Epub 2010 Jun 19.
3
Modification of the substrate specificity of porcine pepsin for the enzymatic production of bovine hide gelatin.猪胃蛋白酶底物特异性的修饰用于酶法生产牛皮明胶。
Protein Sci. 2000 Oct;9(10):1947-59. doi: 10.1110/ps.9.10.1947.
4
Structure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors.使用基于他汀的抑制剂对人组织蛋白酶D进行基于结构的亚位点特异性映射
Protein Sci. 1997 Jul;6(7):1458-66. doi: 10.1002/pro.5560060710.
5
Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.组织蛋白酶D的两种晶体结构：溶酶体靶向信号和活性位点。
EMBO J. 1993 Apr;12(4):1293-302. doi: 10.1002/j.1460-2075.1993.tb05774.x.
6
Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.人组织蛋白酶D天然形式和抑制形式的晶体结构：对溶酶体靶向和药物设计的启示
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6796-800. doi: 10.1073/pnas.90.14.6796.
7
CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type 1 protease with potent antiviral activity.CGP 53437，一种口服生物可利用的1型人类免疫缺陷病毒蛋白酶抑制剂，具有强大的抗病毒活性。
Antimicrob Agents Chemother. 1993 Oct;37(10):2087-92. doi: 10.1128/AAC.37.10.2087.
8
Crystal structure of human pepsin and its complex with pepstatin.人胃蛋白酶及其与胃蛋白酶抑制剂复合物的晶体结构。
Protein Sci. 1995 May;4(5):960-72. doi: 10.1002/pro.5560040516.
本文引用的文献
1
The determination of enzyme inhibitor constants.酶抑制剂常数的测定
Biochem J. 1953 Aug;55(1):170-1. doi: 10.1042/bj0550170.
2
The amino terminal amino acid sequence of human angiotensinogen.人血管紧张素原的氨基末端氨基酸序列。
Biochem Biophys Res Commun. 1981 Apr 30;99(4):1311-5. doi: 10.1016/0006-291x(81)90762-2.
3
Synthesis of analogues of the carboxyl protease inhibitor pepstatin. Effect of structure in subsite P3 on inhibition of pepsin.羧基蛋白酶抑制剂胃蛋白酶抑制剂类似物的合成。P3亚位点结构对胃蛋白酶抑制作用的影响。
J Med Chem. 1982 Jul;25(7):791-5. doi: 10.1021/jm00349a005.
4
Pure human renin. Identification and characterization and of two major molecular weight forms.纯人肾素。两种主要分子量形式的鉴定与表征。
J Biol Chem. 1981 Aug 10;256(15):8164-71.
5
Novel renin inhibitors containing the amino acid statine.含静抑酶氨酸的新型肾素抑制剂。
Nature. 1983;303(5912):81-4. doi: 10.1038/303081a0.
6
A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors.一个描述酶和亚细胞颗粒与紧密结合抑制剂相互作用的稳态动力学的线性方程。
Biochem J. 1972 Apr;127(2):321-33. doi: 10.1042/bj1270321.
7
The interaction of aspartic proteinases with naturally-occurring inhibitors from actinomycetes and Ascaris lumbricoides.天冬氨酸蛋白酶与来自放线菌和蛔虫的天然抑制剂之间的相互作用。
J Enzyme Inhib. 1985;1(1):77-82. doi: 10.3109/14756368509031284.
8
Penicillopepsin, the aspartic proteinase from Penicillium janthinellum: substrate-binding effects and intermediates in transpeptidation reactions.
Biochem Soc Trans. 1985 Dec;13(6):1044-6. doi: 10.1042/bst0131044.
9
Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine.
J Med Chem. 1985 Dec;28(12):1779-90. doi: 10.1021/jm00150a007.
10
A systematic series of synthetic chromophoric substrates for aspartic proteinases.一系列用于天冬氨酸蛋白酶的系统性合成发色底物。
Biochem J. 1986 Aug 1;237(3):899-906. doi: 10.1042/bj2370899.
Zotero 插件