CRYSTAL-STRUCTURE OF ESCHERICHIA-COLI L-ASPARAGINASE, AN ENZYME USED IN CANCER-THERAPY
CRYSTAL-STRUCTURE OF ESCHERICHIA-COLI L-ASPARAGINASE, AN ENZYME USED IN CANCER-THERAPY
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DOI：
10.1073/pnas.90.4.1474
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发表时间：
1993-02-15
影响因子：
11.1
通讯作者：
WLODAWER, A
中科院分区：
文献类型：
--
作者：
SWAIN, AL;JASKOLSKI, M;WLODAWER, A
大肠杆菌天冬酰胺酶II （EC 3.5.1.1）是一种用于治疗急性淋巴细胞白血病的药物（Elspar），通过使用单个重原子衍生物结合分子替代的数据，在2.3埃分辨率下确定了其晶体结构。原子模型被细化到R因子为0.143。该酶是一种具有222对称性的同型四聚体，属于α / β蛋白类。每个亚单位有两个具有独特拓扑特征的域。基于目前的结构证据与之前的生化研究一致，我们提出了属于不同亚基的N端和c端结构域之间的活性位点的位置，并假设Thr-89具有催化作用。
The crystal structure of Escherichia coli asparaginase II (EC 3.5.1.1), a drug (Elspar) used for the treatment of acute lymphoblastic leukemia, has been determined at 2.3 angstrom resolution by using data from a single heavy atom derivative in combination with molecular replacement. The atomic model was refined to an R factor of 0.143. This enzyme, active as a homotetramer with 222 symmetry, belongs to the class of alpha/beta proteins. Each subunit has two domains with unique topological features. On the basis of present structural evidence consistent with previous biochemical studies, we propose locations for the active sites between the N- and C-terminal domains belonging to different subunits and postulate a catalytic role for Thr-89.