Inhibition of angiotensin converting enzyme: dependence on chloride.
Inhibition of angiotensin converting enzyme: dependence on chloride.
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血管紧张素转换酶的抑制：对氯化物的依赖性。
DOI：
10.1021/bi00317a022
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
J. Riordan
中科院分区：
文献类型：
--
作者：
R. Shapiro;J. Riordan
在先前的一篇报道[Shapiro，R.，Holmquist，B.，&Riordan，J.F.(1983)BioChemical 22,3850]中，证明了氯对血管紧张素转换酶(ACE)的激活强烈依赖于底物结构，并根据激活行为确定了三种底物类别。本文研究了9种抑制剂[(D-3-巯基-2-甲基丙酰基)-L-Pro(卡托普利)，N-[1(S)-羧基-3-苯丙基]-L-丙氨酸-L-Pro(MK-422)，L-丙氨酸-L-Pro，N-(苯基磷酰基)-L-Phe-L-Phe，甘氨酸-L-色氨酸，N-[1(S)-羧基-5-氨基戊基]-L-Phe-Gly，L-Phe-L-Arg，Nα-(3-巯基丙酰基)-L-精氨酸和N-alpha-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Lys]含有三类底物的结构特征。300 mM氯化物使所有缓蚀剂的表观KI值显著降低(70-250倍)。然而，抑制作用的增强是在氯离子浓度显著较低的情况下实现的，这些抑制剂的最终精氨酸或赖氨酸比其余的要低。这种可变性与先前发现的底物水解酶的激活是平行的。用慢结合抑制剂MK-422测定了氯化物对稳态酶-抑制剂复合体形成和解离的各个步骤的影响。预稳态分析表明，MK-422和卡托普利的结合遵循(最低限度的)两步机制：(公式；见正文)在快速形成酶-抑制剂复合体之后是缓慢的异构化。
In a previous report [Shapiro, R., Holmquist, B., & Riordan, J. F. (1983) Biochemistry 22, 3850], it was demonstrated that activation of angiotensin converting enzyme (ACE) by chloride is strongly dependent on substrate structure, and three substrate classes were identified on the basis of activation behavior. The present study examines the chloride dependence of the inhibition of ACE by nine inhibitors [(D-3-mercapto-2-methylpropanoyl)-L-Pro (captopril), N-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Pro (MK-422), L-Ala-L-Pro, N-(phenylphosphoryl)-L-Phe-L-Phe, Gly-L-Trp, N-[1(S)-carboxy-5-aminopentyl]-L-Phe-Gly, L-Phe-L-Arg, N alpha-(3-mercaptopropanoyl)-L-Arg, and N alpha-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Lys] containing structural features characteristic of the three classes of substrates. Apparent Ki values for all inhibitors are markedly (70-250-fold) decreased by 300 mM chloride. However, the enhancement of inhibition is achieved at significantly lower chloride concentrations with those inhibitors having an ultimate arginine or lysine than with the remainder. This variability parallels that previously found for activation of substrate hydrolysis. The effect of chloride on the individual steps in the formation and dissociation of the steady-state enzyme-inhibitor complexes was determined with the slow-binding inhibitor MK-422. Pre-steady-state analysis indicates that binding of both MK-422 and captopril follows a (minimally) two-step mechanism: (formula; see text) in which rapid formation of an enzyme-inhibitor complex is followed by a slow isomerization.(ABSTRACT TRUNCATED AT 250 WORDS)
影响因子：
5.8
作者：
D. Rich;E. Sun
通讯作者：
D. Rich;E. Sun
血管紧张素转换酶的阴离子活化：取决于底物的性质。
影响因子：
2.9
作者：
Shapiro,R;Holmquist,B;Riordan,JF
通讯作者：
Riordan,JF