Solution NMR structure of CGL2373, a polyketide cyclase-like protein from Corynebacterium glutamicum
Solution NMR structure of CGL2373, a polyketide cyclase-like protein from Corynebacterium glutamicum
复制标题
来自谷氨酸棒杆菌的聚酮化合物环化酶样蛋白 CGL2373 的溶液 NMR 结构
DOI：
10.1002/prot.25771
复制
发表时间：
2019-07-17
影响因子：
2.9
通讯作者：
Yang, Yunhuang
中科院分区：
文献类型：
--
作者：
Cai, Cong;Nie, Yao;Yang, Yunhuang
来自谷氨酸棒杆菌的蛋白质CGL2373先前被提出是聚酮_cyc2家族的成员，基于来自NMR化学位移分配的氨基酸序列和二级结构特征。本文报道了CGL 2373的溶液NMR结构，它含有三个α-螺旋和一个反平行的β-折叠，并采用螺旋夹折叠。该结构显示出与代表性聚酮环化酶TcmN、WhiE和ZhuI的适度相似性。然而，与这些同源物的结构不同，CGL2373结构看起来像具有大得多的口袋的半开壳，并且代表性聚酮环化酶中用于结合底物和催化芳环形成的关键残基被CGL2373中的不同残基取代。此外，在C.谷氨酸链霉菌含有编码核苷二磷酸激酶、叶酰聚谷氨酸合酶和缬氨酸-tRNA连接酶的额外基因，不同于链霉菌中编码聚酮环化酶的典型基因簇。因此，尽管CGL2373在结构上是聚酮环化酶样蛋白，但其功能可能不同于已知的聚酮环化酶，需要进一步研究。CGL2373的溶液结构为后续功能研究中的电子配体筛选和结合位点鉴定奠定了基础。
Protein CGL2373 from Corynebacterium glutamicum was previously proposed to be a member of the polyketide_cyc2 family, based on amino-acid sequence and secondary structure features derived from NMR chemical shift assignments. We report here the solution NMR structure of CGL2373, which contains three alpha-helices and one antiparallel beta-sheet and adopts a helix-grip fold. This structure shows moderate similarities to the representative polyketide cyclases, TcmN, WhiE, and ZhuI. Nevertheless, unlike the structures of these homologs, CGL2373 structure looks like a half-open shell with a much larger pocket, and key residues in the representative polyketide cyclases for binding substrate and catalyzing aromatic ring formation are replaced with different residues in CGL2373. Also, the gene cluster where the CGL2373-encoding gene is located in C. glutamicum contains additional genes encoding nucleoside diphosphate kinase, folylpolyglutamate synthase, and valine-tRNA ligase, different from the typical gene cluster encoding polyketide cyclase in Streptomyces. Thus, although CGL2373 is structurally a polyketide cyclase-like protein, the function of CGL2373 may differ from the known polyketide cyclases and needs to be further investigated. The solution structure of CGL2373 lays a foundation for in silico ligand screening and binding site identifying in future functional study.