Metallocarboxpeptidases cleave C-terminal residues from peptide substrates and participate in a wide range of physiological processes, but they also contribute to human pathology. On the basis of structural information, we can distinguish between two groups of such metallopeptidases: cowrins and funnelins. Cowrins comprise protozoan, prokaryotic, and mammalian enzymes related to both neurolysin and angiotensin-converting enzyme and their catalytic domains contain 500-700 residues. They are ellipsoidal and traversed horizontally by a long, deep, narrow active-site cleft, in which the C-terminal residues are cut from oligopeptides and unstructured protein tails. The consensus cowrin structure contains a common core of 17 helices and a three-stranded beta-sheet, which participates in substrate binding. This protease family is characterized by a set of spatially conserved amino acids involved in catalysis, HEXXH+EXXS/G+H+Y/R+Y. Funnelins comprise structural relatives of the archetypal bovine carboxypeptidase A1 and feature mammalian, insect and bacterial proteins with strict carboxypeptidase activity. Their approximately 300-residue catalytic domains evince a consensus central eight-stranded beta-sheet flanked on either side by a total of eight helices. They also contain a characteristic set of conserved residues, HXXE+R+NR+H+Y+E, and their active-site clefts are rather shallow and lie at the bottom of a funnel-like cavity. Therefore, these enzymes act on a large variety of well-folded proteins. In both cowrins and funnelins, substrate hydrolysis follows a common general base/acid mechanism. A metal-bound solvent molecule ultimately performs the attack on the scissile peptide bond with the assistance of a strictly conserved glutamate residue.

中文翻译：

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金属羧肽酶的结构和机理。

金属羧肽酶可从肽底物上裂解C末端残基，并参与各种生理过程，但它们也有助于人类病理。根据结构信息，我们可以区分两组这样的金属肽酶：corins和funnelins。蛋白包含与神经溶素和血管紧张素转化酶均相关的原生动物，原核和哺乳动物酶，它们的催化结构域包含500-700个残基。它们是椭圆形的，并在水平方向上被一个长而深，狭窄的活性位点裂开，其中的C端残基从寡肽和未结构化的蛋白质尾部切下。共有的cow蛋白结构包含一个共有17个螺旋的共同核心和一个三链β-折叠，后者参与底物结合。该蛋白酶家族的特征在于参与催化的一组空间保守的氨基酸，HEXXH + EXXS / G + H + Y / R + Y。漏斗素包含原型牛羧肽酶A1的结构亲戚，并具有严格的羧肽酶活性的哺乳动物，昆虫和细菌蛋白为特征。它们的大约300个残基的催化结构域表明，共有的中央八链β-折叠位于两侧，共有八个螺旋。它们还包含一组特征性的保守残基，即HXXE + R + NR + H + Y + E，其活性部位裂口相当浅，位于漏斗状腔的底部。因此，这些酶作用于多种折叠良好的蛋白质。在cow蛋白和漏斗素中，底物水解遵循通用的碱/酸机理。