Inhibition of Mn-2(2+)-arginase by borate leads to the design of a transition state analogue inhibitor, 2(S)-amino-6-boronohexanoic acid
Inhibition of Mn-2(2+)-arginase by borate leads to the design of a transition state analogue inhibitor, 2(S)-amino-6-boronohexanoic acid
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DOI：
10.1021/ja971312d
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发表时间：
1997-08-27
影响因子：
15
通讯作者：
Christianson, DW
中科院分区：
文献类型：
--
作者：
Baggio, R;Elbaum, D;Christianson, DW
鉴于精氨酸催化剂在调节多种代谢途径（如尿素生成1和一氧化氮生物合成2）中的重要性，合成和评价非反应性精氨酸类似物作为可能的酶抑制剂或受体拮抗剂是药物化学的一个快速增长的焦点。2，3迄今为止，只有一种哺乳动物精氨酸催化剂酶，大鼠肝精氨酸酶，已经产生了X射线晶体结构，以指导基于结构的抑制剂设计工作。[4]这种三聚体金属酶在每个亚基的活性位点含有一个双核锰簇，这是最大催化活性所需的。5精氨酸水解通过金属活化的溶剂分子实现，该溶剂分子对称地桥接Mn 2 +
Given the prominence of arginine catabolism in the regulation of diverse metabolic pathways such as ureagenesis1 and nitric oxide biosynthesis, 2 the synthesis and evaluation of nonreactive arginine analogues as possible enzyme inhibitors or receptor antagonists is a rapidly-growing focus of medicinal chemistry. 2, 3 To date, only one enzyme of mammalian arginine catabolism, rat liver arginase, has yielded an X-ray crystal structure to guide structure-based inhibitor design efforts. 4 This trimeric metalloenzyme contains a binuclear manganese cluster in the active site of each subunit required for maximal catalytic activity. 5 Arginine hydrolysis is achieved by a metal-activated solvent molecule that symmetrically bridges the Mn2+