Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase.
Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase.
复制标题
作者：
生物合成酶ForT催化4-氨基-1H-吡唑二羧酸和MgPRPP之间的C-C键形成，以产生福霉素A的C-核苷前体。由ForT催化的转化具有化学意义，因为它是仅有的几个例子之一，其中C-C键的形成通过小的芳香杂环的亲电取代发生。此外，ForT能够区分氨基吡唑二羧酸和其中胺被羟基取代的类似物;鉴于两种分子的空间和电子相似性，这是一项了不起的壮举。在这里，我们报告的生物物理测量，结构生物学和量子化学计算，提供了一个详细的分子图片的ForT催化的C-C键的形成和构象变化，耦合到催化。我们的研究结果为在生物催化生产新型抗病毒C-核苷和C-核苷酸类似物中采用工程化ForT变体奠定了基础。
The biosynthetic enzyme, ForT, catalyses the formation of a C-C bond between 4-amino-1H-pyrazoledicarboxylic acid and MgPRPP to produce a C-nucleoside precursor of formycin A. The transformation catalysed by ForT is of chemical interest because it is one of only a few examples in which C-C bond formation takes place via an electrophilic substitution of a small, aromatic heterocycle. In addition, ForT is capable of discriminating between the aminopyrazoledicarboxylic acid and an analogue in which the amine is replaced by a hydroxyl group; a remarkable feat given the steric and electronic similarities of the two molecules. Here we report biophysical measurements, structural biology and quantum chemical calculations that provide a detailed molecular picture of ForT-catalysed C-C bond formation and the conformational changes that are coupled to catalysis. Our findings set the scene for employing engineered ForT variants in the biocatalytic production of novel, anti-viral C-nucleoside and C-nucleotide analogues.
登录
查看更多内容
影响因子：
8.6
作者：
Hong, Hui;Samborskyy, Markiyan;Leadlay, Peter F.
通讯作者：
Leadlay, Peter F.
影响因子：
2.9
作者：
Krahn, JM;Kim, JH;Smith, JL
通讯作者：
Smith, JL
DOI：
10.1007/s10295-018-2109-2
发表时间：
2019-03-01
影响因子：
3.4
作者：
Maffioli, Sonia I.;Sosio, Margherita;Donadio, Stefano
通讯作者：
Donadio, Stefano
影响因子：
7.3
作者：
Mehellou Y;Rattan HS;Balzarini J
通讯作者：
Balzarini J
影响因子：
7.6
作者：
Eyer, Ludek;Zouharova, Darina;Ruzek, Daniel
通讯作者：
Ruzek, Daniel