L-天冬酰胺酶的结构和生化特性,The FEBS Journal

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L-天冬酰胺酶的结构和生化特性
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-06-01 , DOI: 10.1111/febs.16042
Jacek Lubkowski ₁ , Alexander Wlodawer ₁

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升-Asparaginase（水解酶转换升天冬酰胺至升-天冬氨酸）是在临床实践中被用作其在1978年批准用于儿童急性淋巴细胞白血病治疗方案的组成部分后的抗癌剂的第一个酶。在过去的半个世纪中，对l-天冬酰胺酶的结构和生化特性进行了广泛的研究，提供了从各种来源分离的酶的准确结构描述，并阐明了其活性机制。本综述对“细菌型” l的主要结构和选定的生化特性的当前知识状态进行了批判性评估。- 来自不同生物体的天冬酰胺酶。该酶家族中研究最广泛的成员是与来自大肠杆菌的两种酶之一（通常称为 EcAI 和 EcAII）高度同源的l-天冬酰胺酶。该酶家族的成员，虽然通常被称为细菌型l-天冬酰胺酶，但也已在古细菌或真核生物等不同的生物体中得到鉴定。l超过100种结构模型- 在过去的 30 年中，天冬酰胺酶已保存在蛋白质数据库中。以结构为中心的方法的主要成就之一是阐明了这种利用苏氨酸侧链作为主要亲核试剂的独特水解酶的酶促作用机制的细节。这些酶的其他重要特性的分子基础，例如它们的底物特异性，仍在评估中。的结构和机制研究的结果升-asparaginases正在利用在努力改善这种重要的抗癌药物的临床性能。

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Structural and biochemical properties of L-asparaginase

l-Asparaginase (a hydrolase converting l-asparagine to l-aspartic acid) was the first enzyme to be used in clinical practice as an anticancer agent after its approval in 1978 as a component of a treatment protocol for childhood acute lymphoblastic leukemia. Structural and biochemical properties of l-asparaginases have been extensively investigated during the last half-century, providing an accurate structural description of the enzyme isolated from a variety of sources, as well as clarifying the mechanism of its activity. This review provides a critical assessment of the current state of knowledge of primarily structural, but also selected biochemical properties of ‘bacterial-type’ l-asparaginases from different organisms. The most extensively studied members of this enzyme family are l-asparaginases highly homologous to one of the two enzymes from Escherichia coli (usually referred to as EcAI and EcAII). Members of this enzyme family, although often called bacterial-type l-asparaginases, have been also identified in such divergent organisms as archaea or eukarya. Over 100 structural models of l-asparaginases have been deposited in the Protein Data Bank during the last 30 years. One of the prime achievements of structure-centered approaches was the elucidation of the details of the mechanism of enzymatic action of this unique hydrolase that utilizes a side chain of threonine as the primary nucleophile. The molecular basis of other important properties of these enzymes, such as their substrate specificity, is still being evaluated. Results of structural and mechanistic studies of l-asparaginases are being utilized in efforts to improve the clinical properties of this important anticancer drug.

更新日期：2021-07-19

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