Insights into the catalytic mechanism of PPM Ser/Thr phosphatases from the atomic resolution structures of a mycobacterial enzyme
Insights into the catalytic mechanism of PPM Ser/Thr phosphatases from the atomic resolution structures of a mycobacterial enzyme
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DOI：
10.1016/j.str.2007.06.002
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Alzari, Pedro M.
中科院分区：
文献类型：
--
作者：
Bellinzoni, Marco;Welhenkel, Annemarie;Alzari, Pedro M.
丝氨酸/苏氨酸特异性磷酸酶(PIP)是继蛋白质酪氨酸磷酸酶之后的第二大类催化蛋白质去磷酸化的酶。根据序列相似性、金属离子依赖性和抑制剂敏感性，它们被分为两大家族，称为PPP和PPM。尽管PPM磷酸酶具有广泛的物种分布和广泛的生理作用，但其催化机制主要是通过对人PP2Cα这一单一酶的研究来推断的。在这里，我们报道了腐生菌耻垢分枝杆菌不同配体复合体中可溶性PPM磷酸酶的生化性质和原子分辨结构。这些结构提供了沿催化循环的假定快照，支持在某些重要方面不同于当前接受的模型的缔合反应机制，并强化了PIP收敛进化的假说。
Serine/threonine-specific phosphatases (PIPs) represent, after protein tyrosine phosphatases, the second major class of enzymes that catalyze the dephosphorylation of proteins. They are classed in two large families, known as PPP and PPM, on the basis of sequence similarities, metal ion dependence, and inhibitor sensitivity. Despite their wide species distribution and broad physiological roles, the catalytic mechanism of PPM phosphatases has been primarily inferred from studies of a single enzyme, human PP2C alpha. Here, we report the biochemical characterization and the atomic resolution structures of a soluble PPM phosphatase from the saprophyte Mycobacterium smegmatis in complex with different ligands. The structures provide putative snapshots along the catalytic cycle, which support an associative reaction mechanism that differs in some important aspects from the currently accepted model and reinforces the hypothesis of convergent evolution in PIPs.