当前位置：
X-MOL 学术
›
ACS Catal.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Mechanism of Coordinated Gating and Signal Transduction in Purine Biosynthetic Enzyme Formylglycinamidine Synthetase
ACS Catalysis ( IF 11.3 ) Pub Date : 2022-01-20 , DOI: 10.1021/acscatal.1c05521 Nandini Sharma 1 , Sukhwinder Singh 1 , Ajay S. Tanwar 1 , Jagannath Mondal 2 , Ruchi Anand 1
ACS Catalysis ( IF 11.3 ) Pub Date : 2022-01-20 , DOI: 10.1021/acscatal.1c05521 Nandini Sharma 1 , Sukhwinder Singh 1 , Ajay S. Tanwar 1 , Jagannath Mondal 2 , Ruchi Anand 1
Affiliation
|
Enzymes that harbor transient tunnels have a complex interplay of allostery that links their assembly/disassembly with the catalytic cycle. Here, by employing PurL, a purine biosynthetic enzyme, as a model system, we decipher the mechanism of catalytic coupling, precise orchestration of signal transduction, associated conformational changes, and their link with formation of the transient ammonia tunnel. We show that ammonia passage in PurL is controlled by two gates “mouth-gate” and “end-gate”, with the seed of the allosteric cycle residing at the “end-gate”. It was established that substrate entry at the formylglycinamidine ribonucleotide (FGAM) synthetase domain both initiates end-gate opening and triggers conformational changes in the catalytic loop, which then passes the signal to the glutaminase domain. Molecular dynamics simulations indicate that during the catalytic cycle, the transient tunnel vacillates between open and partially closed states, which gives rise to a breathing ammonia channel that likely acts as a selectivity filter, which occludes solvent and provides directionality for ammonia passage. The mouth-gate network observed here was found to be a conserved feature in class 1 amidotransferases, hinting that a common mode of ammonia control exists across these enzymes.
中文翻译：
嘌呤生物合成酶甲酰甘氨脒合成酶的协同门控和信号转导机制
具有瞬态隧道的酶具有复杂的变构相互作用，将它们的组装/拆卸与催化循环联系起来。在这里，通过使用嘌呤生物合成酶 PurL 作为模型系统，我们破译了催化偶联的机制、信号转导的精确协调、相关的构象变化以及它们与瞬时氨通道形成的联系。我们表明，PurL 中的氨通道由两个门“口门”和“端门”控制，变构循环的种子位于“端门”。已经确定，底物进入甲酰甘氨酰胺核糖核苷酸 (FGAM) 合成酶结构域既会启动端门打开，又会触发催化环中的构象变化，然后将信号传递到谷氨酰胺酶结构域。分子动力学模拟表明，在催化循环期间，瞬态隧道在开放和部分闭合状态之间真空摇动，这导致呼吸氨通道，其可能用作选择性过滤器，该呼吸氨通道可作为选择性过滤器，该呼吸氨通道堵塞溶剂并为氨通道提供方向性。发现此处观察到的口门网络是 1 类氨基转移酶中的一个保守特征，暗示这些酶中存在一种常见的氨控制模式。
更新日期：2022-02-04
中文翻译：
嘌呤生物合成酶甲酰甘氨脒合成酶的协同门控和信号转导机制
具有瞬态隧道的酶具有复杂的变构相互作用，将它们的组装/拆卸与催化循环联系起来。在这里，通过使用嘌呤生物合成酶 PurL 作为模型系统，我们破译了催化偶联的机制、信号转导的精确协调、相关的构象变化以及它们与瞬时氨通道形成的联系。我们表明，PurL 中的氨通道由两个门“口门”和“端门”控制，变构循环的种子位于“端门”。已经确定，底物进入甲酰甘氨酰胺核糖核苷酸 (FGAM) 合成酶结构域既会启动端门打开，又会触发催化环中的构象变化，然后将信号传递到谷氨酰胺酶结构域。分子动力学模拟表明，在催化循环期间，瞬态隧道在开放和部分闭合状态之间真空摇动，这导致呼吸氨通道，其可能用作选择性过滤器，该呼吸氨通道可作为选择性过滤器，该呼吸氨通道堵塞溶剂并为氨通道提供方向性。发现此处观察到的口门网络是 1 类氨基转移酶中的一个保守特征，暗示这些酶中存在一种常见的氨控制模式。
京公网安备 11010802027423号