Ito Makoto, Okino Nozomu, Tani Motohiro
Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan.
Department of Chemistry, Faculty of Science, Kyushu University, 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan.
Biochim Biophys Acta. 2014 May;1841(5):682-91. doi: 10.1016/j.bbalip.2013.09.008. Epub 2013 Sep 21.
Ceramidase (CDase) is an enzyme that hydrolyzes the N-acyl linkage between the sphingoid base and fatty acid of ceramide. These enzymes are classified into three distinct groups, acid (Asah1), neutral (Asah2), and alkaline (Asah3) CDases, based on their primary structure and optimum pH. Acid CDase catabolizes ceramide in lysosomes and is found only in vertebrates. In contrast, the distribution of neutral and alkaline CDases is broad, with both being found in species ranging from lower eukaryotes to mammals; however, only neutral CDase is found in prokaryotes, including some pathogenic bacteria. Neutral CDase is thought to have gained a specific domain (mucin box) in the N-terminal region after the vertebrate split, allowing the enzyme to be stably expressed at the plasma membrane as a type II membrane protein. The X-ray crystal structure of neutral CDase was recently solved, uncovering a unique structure and reaction mechanism for the enzyme. Neutral CDase contains a zinc ion in the active site that functions as a catalytic center, and the hydrolysis of the N-acyl linkage in ceramide proceeds through a mechanism that is similar to that described for zinc-dependent carboxypeptidase. This review describes the structure, reaction mechanism, and biological functions of neutral CDase in association with the molecular evolution, topology, and mechanical conformation. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.
神经酰胺酶（CDase）是一种能够水解神经酰胺中鞘氨醇碱基与脂肪酸之间N - 酰基连接的酶。根据其一级结构和最适pH值，这些酶可分为三个不同的组，即酸性（Asah1）、中性（Asah2）和碱性（Asah3）神经酰胺酶。酸性神经酰胺酶在溶酶体中分解代谢神经酰胺，且仅在脊椎动物中发现。相比之下，中性和碱性神经酰胺酶的分布广泛，在从低等真核生物到哺乳动物的各种物种中均有发现；然而，仅在原核生物（包括一些致病细菌）中发现了中性神经酰胺酶。据认为，中性神经酰胺酶在脊椎动物分化后，其N端区域获得了一个特定结构域（粘蛋白盒），使得该酶能够作为II型膜蛋白在质膜上稳定表达。中性神经酰胺酶的X射线晶体结构最近已得到解析，揭示了该酶独特的结构和反应机制。中性神经酰胺酶的活性位点含有一个锌离子，其作为催化中心发挥作用，神经酰胺中N - 酰基连接的水解过程与锌依赖性羧肽酶所描述的机制相似。本综述结合分子进化、拓扑结构和机械构象，描述了中性神经酰胺酶的结构、反应机制和生物学功能。本文是名为“鞘脂生物学新前沿”的特刊的一部分。
