Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase

doi:10.1038/s41467-023-40455-y

CORC > 海洋研究所 > 中国科学院海洋研究所 > 实验海洋生物学重点实验室

	Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase
	Wang, Chongyang 1,2,3,4; Liu, Changshui 1,2,3; Zhu, Xiaochuan 1,2; Peng, Quancai 5; Ma, Qingjun 1,2,3,4,5
刊名	NATURE COMMUNICATIONS
	2023-08-09
卷号	14 期号:1 页码:11
DOI	10.1038/s41467-023-40455-y
通讯作者	Ma, Qingjun(qma@qdio.ac.cn)
英文摘要	Vibrio dual lipases/transferases are virulence-related enzymes, with both substrate and catalytic promiscuity. Wang et al reveal their prominent structural flexibility, proposing a catalytic site tuning mechanism underlying enzyme promiscuity. Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the "Ser-His-Asp" catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a "catalytic site tuning" mechanism to expand the mechanistic paradigm of enzyme promiscuity.
资助项目	Qingdao Innovation Leadership Program[2015ASTP] ; Pilot National Laboratory for Marine Science and Technology[18-1-2-12-zhc]
WOS关键词	ENZYME PROMISCUITY ; STRUCTURAL BASIS ; PHOSPHOLIPASE ; PURIFICATION ; HEMOLYSIN ; PARAHAEMOLYTICUS ; IDENTIFICATION ; PATHOGENICITY ; ACTIVATION ; MECHANISM
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PORTFOLIO
WOS记录号	WOS:001045317100017
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/182774]
专题	海洋研究所_实验海洋生物学重点实验室
通讯作者	Ma, Qingjun
作者单位	1.Chinese Acad Sci, Qingdao, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China 3.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Mega Sci, Qingdao, Peoples R China
推荐引用方式 GB/T 7714	Wang, Chongyang,Liu, Changshui,Zhu, Xiaochuan,et al. Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase[J]. NATURE COMMUNICATIONS,2023,14(1):11.
APA	Wang, Chongyang,Liu, Changshui,Zhu, Xiaochuan,Peng, Quancai,&Ma, Qingjun.(2023).Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.NATURE COMMUNICATIONS,14(1),11.
MLA	Wang, Chongyang,et al."Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase".NATURE COMMUNICATIONS 14.1(2023):11.