MODULATION OF GLUTAMINE SYNTHETASE ADENYLYLATION AND DEADENYLYLATION IS MEDIATED BY METABOLIC TRANSFORMATION OF PII-REGULATORY PROTEIN
MODULATION OF GLUTAMINE SYNTHETASE ADENYLYLATION AND DEADENYLYLATION IS MEDIATED BY METABOLIC TRANSFORMATION OF PII-REGULATORY PROTEIN
复制标题
DOI：
10.1073/pnas.68.12.2949
复制
发表时间：
1971-01-01
影响因子：
11.1
通讯作者：
STADTMAN, ER
中科院分区：
文献类型：
--
作者：
BROWN, MS;SEGAL, A;STADTMAN, ER
早期的研究表明，大肠杆菌谷氨酰胺合成酶的两个蛋白组分PI和PII与腺苷酰化和去腺苷酰化有关（EC 6.3.1.2）。PI本身催化腺苷酰化和去腺苷酰化，但其活性受PII蛋白和谷氨酰胺、2-酮戊二酸、ATP和UTP调节。PII蛋白以两种形式存在：一种形式PII-AT在不存在谷氨酰胺的情况下刺激PI催化的腺苷酰化活性，并使该活性对2-酮戊二酸的抑制非常敏感;它不影响去腺苷酰化活性。另一种形式PII-DA仅在谷氨酰胺存在时刺激腺苷酸化，并且还刺激PI的去腺苷酸化活性，其随后依赖于ATP和2-酮戊二酸的存在。PII-AT转化为PII-DA需要UTP、ATP和2-酮戊二酸的存在;它由PI制剂中存在的酶催化。UTP可能直接参与这种转化，因为通过Sephadex G-100过滤重新分离的PII-DA组分含有少量缺乏UTP的γ-磷酰基的结合尿苷衍生物。蛇毒磷酸二酯酶处理可破坏PII-DA的活性，但不破坏PII-AT的活性。ATP和2-酮戊二酸显然作为变构效应物用于PII-AT向PI-DA的转化。
Earlier studies showed that two protein components, PIand PII, are concerned with the adenylylation and deadenylylation ofEscherichia coliglutamine synthetase (EC 6.3.1.2). PIby itself catalyzes both adenylylation and deadenylylation, but its activity is modulated by the PII-protein and by glutamine, 2-oxoglutarate, ATP, and UTP, The PII-protein exists in two forms: one form, PII-AT, stimulates PI-catalyzed adenylylation activity in the absence of glutamine and makes this activity very sensitive to inhibition by 2-oxoglutarate; it does not affect deadenylylation activity. The other form, PII-DA, stimulates adenylylation only if glutamine is present, and also stimulates the deadenylylation activity of PI, which is then dependent upon the presence of ATP and 2-oxoglutarate. Conversion of PII-AT to PII-DA requires the presence of UTP, ATP, and 2-oxoglutarate; it is catalyzed by an enzyme present in PIpreparations. UTP may be directly involved in this conversion since PII-DA fractions reisolated by filtration through Sephadex G-100 contain small quantities of a bound uridine derivative that lacks the γ-phosphoryl group of UTP. The activity of PII-DA, but not of PII-AT, is destroyed by treatment with snake-venom phosphodiesterase. ATP and 2-oxoglutarate apparently function as allosteric effectors for the conversion of PII-AT to PI-DA.