Structure of protein O-mannose kinase reveals a unique active site   architecture

doi:10.7554/eLife.22238

CORC > 北京大学 > 化学与分子工程学院

	Structure of protein O-mannose kinase reveals a unique active site architecture
	Zhu, Qinyu ; Venzke, David ; Walimbe, Ameya S. ; Anderson, Mary E. ; Fu, Qiuyu ; Kinch, Lisa N. ; Wang, Wei ; Chen, Xing ; Grishin, Nick V. ; Huang, Niu ; Yu, Liping ; Dixon, Jack E. ; Campbell, Kevin P. ; Xiao, Junyu
刊名	ELIFE
	2016
关键词	ALPHA-DYSTROGLYCAN CRYSTAL-STRUCTURE MUSCULAR-DYSTROPHY RIBITOL-PHOSPHATE CATALYTIC DOMAIN LAMININ-BINDING VIRUS ENTRY PHOSPHORYLATION RECEPTOR SYSTEM
DOI	10.7554/eLife.22238
英文摘要	The 'pseudokinase' SgK196 is a protein O-mannose kinase (POMK) that catalyzes an essential phosphorylation step during biosynthesis of the laminin-binding glycan on alpha-dystroglycan. However, the catalytic mechanism underlying this activity remains elusive. Here we present the crystal structure of Danio rerio POMK in complex with Mg2+ ions, ADP, aluminum fluoride, and the GalNAc-beta 3-GlcNAc-beta 4-Man trisaccharide substrate, thereby providing a snapshot of the catalytic transition state of this unusual kinase. The active site of POMK is established by residues located in non-canonical positions and is stabilized by a disulfide bridge. GalNAc-beta 3-GlcNAc-beta 4-Man is recognized by a surface groove, and the GalNAc-beta 3-GlcNAc moiety mediates the majority of interactions with POMK. Expression of various POMK mutants in POMK knockout cells further validated the functional requirements of critical residues. Our results provide important insights into the ability of POMK to function specifically as a glycan kinase, and highlight the structural diversity of the human kinome.; National Institute of Diabetes and Digestive and Kidney Diseases [DK18849, DK18024]; Howard Hughes Medical Institute; Paul D. Wellstone Muscular Dystrophy Cooperative Research Center [1U54NS053672]; National Natural Science Foundation of China [31570735]; National Key Research and Development Plan of China [2016YFC0906000]; SCI(E); ARTICLE; campbell@uiowa.edu; junyuxiao@pku.edu.cn; 5
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/458380]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Zhu, Qinyu,Venzke, David,Walimbe, Ameya S.,et al. Structure of protein O-mannose kinase reveals a unique active site architecture[J]. ELIFE,2016.
APA	Zhu, Qinyu.,Venzke, David.,Walimbe, Ameya S..,Anderson, Mary E..,Fu, Qiuyu.,...&Xiao, Junyu.(2016).Structure of protein O-mannose kinase reveals a unique active site architecture.ELIFE.
MLA	Zhu, Qinyu,et al."Structure of protein O-mannose kinase reveals a unique active site architecture".ELIFE (2016).