Structural insights into a new substrate binding mode of a histidine acid phosphatase from Legionella pneumophila.
Structural insights into a new substrate binding mode of a histidine acid phosphatase from Legionella pneumophila.
复制标题
DOI：
10.1016/j.bbrc.2020.12.070
复制
发表时间：
2021-01
影响因子：
3.1
通讯作者：
Yu Guo;Dan Zhou;Hui Zhang;N. Zhang;Xiaoyu Qi;Xiaofang Chen;Qi Chen;Jing Li;H. Ge;Y. Teng
中科院分区：
文献类型：
--
作者：
Yu Guo;Dan Zhou;Hui Zhang;N. Zhang;Xiaoyu Qi;Xiaofang Chen;Qi Chen;Jing Li;H. Ge;Y. Teng
MapA是一种来自嗜肺军团菌的组氨酸酸性磷酸酶（HAP），其催化磷酸单酯的磷酰基被活性位点组氨酸羟基化。几种结构的HAP，包括MapA，在复杂的抑制剂酒石酸盐已被解决和底物结合隧道确定，然而，底物识别机制仍然未知。为了深入了解底物识别机制，分别以2.2和2.6 μ m分辨率解析了apo-MapA和MapAD 281 A突变体与5′-AMP复合物的晶体结构。MapAD 281 A/5′-AMP复合物的结构表明，5′-AMP完全适合底物结合通道，其中核糖部分的2′-羟基由Glu 201稳定，腺嘌呤部分夹在His 205和Phe 237之间。这是HAP/AMP复合物的第二种结构，在活性位点以独特的方式与5′-AMP结合。该结构提出了一种新的HAPs底物识别机制。
MapA is a histidine acid phosphatase (HAP) fromLegionella pneumophilathat catalyzes the hydroxylation of a phosphoryl group from phosphomonoesters by an active-site histidine. Several structures of HAPs, including MapA, in complex with the inhibitor tartrate have been solved and the substrate binding tunnel identified; however, the substrate recognition mechanism remains unknown. To gain insight into the mechanism of substrate recognition, the crystal structures of apo-MapA and the MapAD281Amutant in complex with 5′-AMP were solved at 2.2 and 2.6 Å resolution, respectively. The structure of the MapAD281A/5′-AMP complex reveals that the 5′-AMP fits fully into the substrate binding tunnel, with the 2′-hydroxyl group of the ribose moiety stabilized by Glu201 and the adenine moiety sandwiched between His205 and Phe237. This is the second structure of a HAP/AMP complex solved with 5′-AMP binding in a unique manner in the active site. The structure presents a new substrate recognition mechanism of HAPs.