CONFORMATIONAL-CHANGES IN ORNITHINE DECARBOXYLASE ENABLE RECOGNITION BY ANTIZYME
CONFORMATIONAL-CHANGES IN ORNITHINE DECARBOXYLASE ENABLE RECOGNITION BY ANTIZYME
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DOI：
10.1016/0167-4838(90)90109-s
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发表时间：
1990-01-19
期刊：
影响因子：
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通讯作者：
CHEN, HJ
中科院分区：
文献类型：
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作者：
MITCHELL, JLA;CHEN, HJ
多胺诱导的哺乳动物鸟氨酸脱羧酶（l -鸟氨酸羧化酶，EC 4.1.1.17） （ODC）的快速降解被认为是由一种称为抗酶的小的ODC结合蛋白的可用性控制的。在这项研究中，我们研究了抗酶在各种生理状态下结合ODC蛋白的能力。特别是，低温、NaCl、亚精胺以及辅酶和底物的剥夺都促进了酶-抗酶复合物的形成，并且都促进了ODC同型二聚体的解离。相反，维持活性ODC同二聚体状态的条件可以防止ODC的抗酶结合和失活。此外，二氟甲基鸟氨酸或磷酸盐对ODC活性位点附近的共价修饰也增加了其抗酶能力。这些结果表明，ODC降解的初始信号实际上可能是酶的微妙构象变化，使抗酶与酶结合，并可能随后促进其降解。
Rapid, polyamine-induced degradation of mammalian ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) (ODC) is thought to be controlled by the availability of a small, ODC-binding protein termed antizyme. In this study we have investigated the ability of antizyme to bind ODC protein in various altered physiological states. In particular, cold, NaCl, spermidine and deprivation of coenzyme and substrate enhance enzyme-antizyme complex formation and are all found to promote ODC homodimer dissociation. Conversely, conditions that maintain the active ODC homodimer state prevent antizyme binding and inactivation of ODC. Further, covalent modification of ODC near its active site by difluoromethylornithine or phosphate also increases it antizyme. These results suggest that the initial signal in ODC degradation may actually be a subtle conformational change in the enzyme that enables antizyme to bind to the enzyme and may subsequently facilitate its degradation.