Crystal structure of the dinuclear zinc aminopeptidase PepV from Lactobacillus delbrueckii unravels its preference for dipeptides
Crystal structure of the dinuclear zinc aminopeptidase PepV from Lactobacillus delbrueckii unravels its preference for dipeptides
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DOI：
10.1016/s0969-2126(02)00805-5
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发表时间：
2002-08-01
期刊：
影响因子：
5.7
通讯作者：
Maskos, K
中科院分区：
文献类型：
--
作者：
Jozic, D;Bourenkow, G;Maskos, K
来自德氏乳杆菌的PepV是一种双核锌肽酶，已被表征为非特异性氨基二肽酶。PepV与次膦酸抑制剂Asppsi[PO2CH2]AlaOH（二肽底物模拟物）复合的晶体结构揭示了“催化结构域”和“盖结构域”，它们一起形成捕获抑制剂的内部活性位点空腔。催化结构域在拓扑学上类似于来自氨基肽酶和羧肽酶的催化结构域。然而，盖结构域在相关酶中是独特的。与其他相关的外肽酶相比，PepV识别并固定二肽骨架，而侧链不被特异性探测并且可以变化，使其成为非特异性二肽酶。共结晶抑制剂说明了两个催化锌离子的两个作用，即稳定的四面体中间体和催化水分子的活化。
PepV from Lactobacillus delbrueckii, a dinuclear zinc peptidase, has been characterized as an unspecific amino dipeptidase. The crystal structure of PepV in complex with the phosphinic inhibitor Asppsi[PO2CH2]AlaOH, a dipeptide substrate mimetic, reveals a "catalytic domain" and a "lid domain," which together form an internal active site cavity that traps the inhibitor. The catalytic domain is topologically similar to catalytic domains from amino- and carboxypeptidases. However, the lid domain is unique among the related enzymes. In contrast to the other related exopeptidases, PepV recognizes and fixes the dipeptide backbone, while the side chains are not specifically probed and can vary, rendering it a nonspecific dipeptidase. The cocrystallized inhibitor illustrates the two roles of the two catalytic zinc ions, namely stabilization of the tetrahedral intermediate and activation of the catalytic water molecule.