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首页> 外文期刊>Journal of enzyme inhibition >Glycosylasparaginase inhibition studies: competitive inhibitors, transition state mimics, noncompetitive inhibitors.
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Glycosylasparaginase inhibition studies: competitive inhibitors, transition state mimics, noncompetitive inhibitors.

机译：糖基葡聚糖酶抑制研究：竞争性抑制剂，过渡态模拟物，非竞争性抑制剂。

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摘要

Glycosylasparaginase catalyzes the hydrolysis of the N-glycosylic bond between asparagine and N-acetylglucosamine in the catabolism of N-linked glycoproteins. Previously only three competitive inhibitors, one noncompetitive inhibitor, and one irreversible inhibitor of glycosylasparaginase activity had been reported. Using human glycosylasparaginase from human amniotic fluid, L-aspartic acid and four of its analogues, where the alpha-amino group was substituted with a chloro, bromo, methyl or hydrogen, were competitive inhibitors having Ki values between 0.6-7.7 mM. These results provide supporting evidence for a proposed intramolecular autoproteolytic activation reaction. A proposed phosphono transition state mimic and a sulfo transition state mimic were competitive inhibitors with Ki values 0.9 mM and 1.4 mM, respectively. These results support a mechanism for the enzyme-catalyzed reaction involving formation of a tetrahedral high-energy intermediate. Three analogues of the natural substrate were noncompetitive inhibitors with Ki values between 0.56-0.75 mM, indicating the presence of a second binding site that may recognize (substituted)acetamido groups.
机译：糖基葡聚糖天冬酰胺酶催化N-连接的糖蛋白分解代谢中的天冬酰胺和N-乙酰基葡糖胺之间的N-糖基键的水解。以前，仅报道了三种竞争性抑制剂，一种非竞争性抑制剂和一种不可逆的糖基半乳糖苷酶活性抑制剂。使用来自人羊水的人糖基葡聚糖酶，L-天冬氨酸及其四个类似物（竞争性抑制剂）的Ki值在0.6-7.7 mM之间，其中α-氨基被氯，溴，甲基或氢取代。这些结果为提出的分子内自蛋白水解活化反应提供了支持证据。拟议的膦酰基过渡态模拟物和磺基过渡态模拟物是竞争性抑制剂，其Ki值分别为0.9 mM和1.4 mM。这些结果支持了涉及形成四面体高能中间体的酶催化反应的机制。天然底物的三个类似物是非竞争性抑制剂，Ki值在0.56-0.75 mM之间，表明存在第二个结合位点，该结合位点可以识别（取代）乙酰氨基。

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