Angiotensin-I-converting enzyme and its relatives.
Angiotensin-I-converting enzyme and its relatives.
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DOI：
10.1186/gb-2003-4-8-225
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发表时间：
2003
期刊：
影响因子：
12.3
通讯作者：
Riordan JF
中科院分区：
文献类型：
--
作者：
Riordan JF
血管紧张素I转换酶（ACE）是一种单体、膜结合、锌和氯化物依赖的蛋白质，它催化十肽血管紧张素I转化为八肽血管紧张素II。ACE是调节血压系统的关键部分，最近的x射线结构可能有助于设计改进的ACE抑制剂。血管紧张素- 1转换酶（ACE）是一种单体、膜结合、锌和氯依赖的肽基二肽酶，通过去除羧基末端的二肽，催化十肽血管紧张素I转化为八肽血管紧张素II。长期以来，人们一直认为ACE是肾素血管紧张素系统调节血压的关键部分，ACE抑制剂对高血压的治疗很重要。这种酶在人体中有两种形式，一种是普遍存在的体细胞ACE，另一种是精子特有的生发ACE，它们都是由同一基因通过不同启动子转录而编码的。体细胞ACE有两个具有不同催化特性的串联活性位点，而生发ACE只有一个活性位点，其功能在很大程度上是未知的。最近，在人类中发现了ACE的同源物ACE2，它与ACE的不同之处在于它是一种羧基肽酶，优先去除羧基末端的疏水氨基酸或碱性氨基酸；它似乎对心脏功能很重要。ACE的同系物（也被称为M2谷胱甘肽家族的成员）已经在许多物种中被发现，甚至在那些既没有心血管系统也不合成血管紧张素的物种中。据报道，来自果蝇的一种去糖基化的生发ACE和一种相关酶的x射线结构显示，活性位点位于中心空腔的深处。基于结构的药物设计针对体细胞ACE的单个活性位点，可能导致新一代的ACE抑制剂，其副作用比现有的抑制剂更少。
Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound, zinc- and chloride-dependent protein that catalyzes the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II. ACE is a key part of the system that regulates blood pressure, and recent X-ray structures may help design improved ACE inhibitors. Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound, zinc- and chloride-dependent peptidyl dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a carboxy-terminal dipeptide. ACE has long been known to be a key part of the renin angiotensin system that regulates blood pressure, and ACE inhibitors are important for the treatment of hypertension. There are two forms of the enzyme in humans, the ubiquitous somatic ACE and the sperm-specific germinal ACE, both encoded by the same gene through transcription from alternative promoters. Somatic ACE has two tandem active sites with distinct catalytic properties, whereas germinal ACE, the function of which is largely unknown, has just a single active site. Recently, an ACE homolog, ACE2, has been identified in humans that differs from ACE in being a carboxypeptidase that preferentially removes carboxy-terminal hydrophobic or basic amino acids; it appears to be important in cardiac function. ACE homologs (also known as members of the M2 gluzincin family) have been found in a wide variety of species, even in those that neither have a cardiovascular system nor synthesize angiotensin. X-ray structures of a truncated, deglycosylated form of germinal ACE and a related enzyme from Drosophila have been reported, and these show that the active site is deep within a central cavity. Structure-based drug design targeting the individual active sites of somatic ACE may lead to a new generation of ACE inhibitors, with fewer side-effects than currently available inhibitors.
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