Crystal structure determination of a chimeric FabF by XRD

doi:10.1007/s41365-017-0281-0

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Crystal structure determination of a chimeric FabF by XRD
	Li, Ke 1,2; Li, Li 2; Xu, Ye-Chun2
刊名	NUCLEAR SCIENCE AND TECHNIQUES
	2017-09
卷号	28 期号:9
关键词	FabF Chimera X-ray diffraction Crystal structure determination
ISSN号	1001-8042
DOI	10.1007/s41365-017-0281-0
文献子类	Article
英文摘要	Beta-ketoacyl-acyl-carrier-protein synthase II, an important enzyme in biosynthesis of bacterial fatty acid, is an attractive target in antibacterial drug design. Platensimycin (PTM), produced by Streptomyces platensis, has a strong, broad-spectrum Gram-positive antibacterial activity by selectively targeting to FabF but exhibits no inhibition to the FabF from Streptomyces platensis (spFabF). To study the self-resistance mechanism within the PTM-producing strain and provide hint for development of novel antibiotics, it is imperative to solve the structure of spFabF and elucidate the difference between spFabF and other FabFs which are not resistant to PTM. To this end, we constructed four chimeric FabFs based on the sequence of spFabF and its homologous protein after the expression of wide-type spFabF was failed. The crystal structure of one chimera, js(200)FabF, of 91.2% sequence identity to spFabF, was solved. A structure comparison of js(200)FabF with a PTM-bound FabF suggested that three loops nearby the catalytic site might play key roles in preventing the binding of PTM to spFabF. The results provide an encouraging basis for further studies on the self-resistance mechanism and structure-based design of novel antibiotics targeting FabFs.
资助项目	National Natural Science Foundation of China[81502987] ; National Natural Science Foundation of China[81422047]
WOS关键词	FATTY-ACID SYNTHASE ; STREPTOMYCES-PLATENSIS ; BIOSYNTHESIS ; INHIBITOR
WOS研究方向	Nuclear Science & Technology ; Physics
语种	英语
出版者	SPRINGER SINGAPORE PTE LTD
WOS记录号	WOS:000408853800004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272508]
专题	药物发现与设计中心
通讯作者	Xu, Ye-Chun
作者单位	1.Shanghai Univ, Coll Sci, 99 Shangda Rd, Shanghai 200444, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Ke,Li, Li,Xu, Ye-Chun. Crystal structure determination of a chimeric FabF by XRD[J]. NUCLEAR SCIENCE AND TECHNIQUES,2017,28(9).
APA	Li, Ke,Li, Li,&Xu, Ye-Chun.(2017).Crystal structure determination of a chimeric FabF by XRD.NUCLEAR SCIENCE AND TECHNIQUES,28(9).
MLA	Li, Ke,et al."Crystal structure determination of a chimeric FabF by XRD".NUCLEAR SCIENCE AND TECHNIQUES 28.9(2017).