当前位置: X-MOL 学术Acta Cryst. F › 论文详情
Structural basis for the substrate recognition of aminoglycoside 7''-phosphotransferase-Ia from Streptomyces hygroscopicus.
Acta Crystallographica Section F ( IF 0.968 ) Pub Date : 2019-08-28 , DOI: 10.1107/s2053230x19011105
Mihoko Takenoya,Tatsuro Shimamura,Ryuji Yamanaka,Yuya Adachi,Shinsaku Ito,Yasuyuki Sasaki,Akira Nakamura,Shunsuke Yajima

Hygromycin B (HygB) is one of the aminoglycoside antibiotics, and it is widely used as a reagent in molecular-biology experiments. Two kinases are known to inactivate HygB through phosphorylation: aminoglycoside 7''-phosphotransferase-Ia [APH(7'')-Ia] from Streptomyces hygroscopicus and aminoglycoside 4-phosphotransferase-Ia [APH(4)-Ia] from Escherichia coli. They phosphorylate the hydroxyl groups at positions 7'' and 4 of the HygB molecule, respectively. Previously, the crystal structure of APH(4)-Ia was reported as a ternary complex with HygB and 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). To investigate the differences in the substrate-recognition mechanism between APH(7'')-Ia and APH(4)-Ia, the crystal structure of APH(7'')-Ia complexed with HygB is reported. The overall structure of APH(7'')-Ia is similar to those of other aminoglycoside phosphotransferases, including APH(4)-Ia, and consists of an N-terminal lobe (N-lobe) and a C-terminal lobe (C-lobe). The latter also comprises a core and a helical domain. Accordingly, the APH(7'')-Ia and APH(4)-Ia structures fit globally when the structures are superposed at three catalytically important conserved residues, His, Asp and Asn, in the Brenner motif, which is conserved in aminoglycoside phosphotransferases as well as in eukaryotic protein kinases. On the other hand, the phosphorylated hydroxyl groups of HygB in both structures come close to the Asp residue, and the HygB molecules in each structure lie in opposite directions. These molecules were held by the helical domain in the C-lobe, which exhibited structural differences between the two kinases. Furthermore, based on the crystal structures of APH(7'')-Ia and APH(4)-Ia, some mutated residues in their thermostable mutants reported previously were located at the same positions in the two enzymes.
更新日期:2019-11-01

 

全部期刊列表>>
AI核心技术
10years
材料学研究精选
Springer Nature Live 产业与创新线上学术论坛
胸腔和胸部成像专题
自然科研论文编辑服务
ACS ES&T Engineering
ACS ES&T Water
屿渡论文,编辑服务
杨超勇
周一歌
华东师范大学
段炼
清华大学
廖矿标
李远
跟Nature、Science文章学绘图
隐藏1h前已浏览文章
中洪博元
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
福州大学
南京大学
王杰
左智伟
电子显微学
何凤
洛杉矶分校
吴杰
赵延川
试剂库存
天合科研
down
wechat
bug