气候变化领域集成服务门户(CCPortal): Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis

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DOI	10.1073/pnas.2019220118
	Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis
	Pluvinage B.; Ficko-Blean E.; Noach I.; Stuart C.; Thompson N.; McClure H.; Buenbrazo N.; Wakarchuk W.; Boraston A.B.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	A challenge faced by peptidases is the recognition of highly diverse substrates. A feature of some peptidase families is the capacity to specifically use post-translationally added glycans present on their protein substrates as a recognition determinant. This is ultimately critical to enabling peptide bond hydrolysis. This class of enzyme is also frequently large and architecturally sophisticated. However, the molecular details underpinning glycan recognition by these O-glycopeptidases, the importance of these interactions, and the functional roles of their ancillary domains remain unclear. Here, using the Clostridium perfringens ZmpA, ZmpB, and ZmpC M60 peptidases as model proteins, we provide structural and functional insight into how these intricate proteins recognize glycans as part of catalytic and noncatalytic substrate recognition. Structural, kinetic, and mutagenic analyses support the key role of glycan recognition within the M60 domain catalytic site, though they point to ZmpA as an apparently inactive enzyme. Wider examination of the Zmp domain content reveals noncatalytic carbohydrate binding as a feature of these proteins. The complete three-dimensional structure of ZmpB provides rare insight into the overall molecular organization of a highly multimodular enzyme and reveals how the interplay of individual domain function may influence biological activity. O-glycopeptidases frequently occur in host-adapted microbes that inhabit or attack mucus layers. Therefore, we anticipate that these results will be fundamental to informing more detailed models of how the glycoproteins that are abundant in mucus are destroyed as part of pathogenic processes or liberated as energy sources during normal commensal lifestyles. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Clostridium; Mucin; Multimodular; O-glycan; Structure
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180338
作者单位	Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 2Y2, Canada; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada
推荐引用方式 GB/T 7714	Pluvinage B.,Ficko-Blean E.,Noach I.,et al. Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis[J],2021,118(10).
APA	Pluvinage B..,Ficko-Blean E..,Noach I..,Stuart C..,Thompson N..,...&Boraston A.B..(2021).Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Pluvinage B.,et al."Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).