The crystal structure of Mycobacterium tuberculosis adenylate kinase in complex with two molecules of ADP and Mg2+ supports an associative mechanism for phosphoryl transfer
The crystal structure of Mycobacterium tuberculosis adenylate kinase in complex with two molecules of ADP and Mg2+ supports an associative mechanism for phosphoryl transfer
复制标题
DOI：
10.1110/ps.062163406
复制
发表时间：
2006-06-01
期刊：
影响因子：
8
通讯作者：
Alzari, Pedro M.
中科院分区：
文献类型：
--
作者：
Bellinzoni, Marco;Haouz, Ahmed;Alzari, Pedro M.
在1.9埃分辨率下测定了结核分枝杆菌腺苷酸激酶(MtAK)与两个ADP分子和镁离子形成的络合物的晶体结构。与没有底物时得到的酶的溶液结构进行比较，发现底物结合时LID和NMP结合域的构象发生了显著的变化。三元复合体表示酶在反向反应(ATP合成)开始时的状态。该结构与受体ADP分子的末端氧对给体底物的β-磷酸直接亲核攻击是一致的，活性中心中正电荷的几何构型和分布都支持磷酰化转移缔合机制的假说。
The crystal structure of Mycobacterium tuberculosis adenylate kinase (MtAK) in complex with two ADP molecules and Mg2+ has been determined at 1.9 angstrom resolution. Comparison with the solution structure of the enzyme, obtained in the absence of substrates, shows significant conformational changes of the LID and NMP-binding domains upon substrate binding. The ternary complex represents the state of the enzyme at the start of the backward reaction (ATP synthesis). The structure is consistent with a direct nucleophilic attack of a terminal oxygen from the acceptor ADP molecule on the beta-phosphate from the donor substrate, and both the geometry and the distribution of positive charge in the active site support the hypothesis of an associative mechanism for phosphoryl transfer.