气候变化领域集成服务门户(CCPortal): Decoding allosteric regulation by the acyl carrier protein

CCPortal

DOI	10.1073/pnas.2025597118
	Decoding allosteric regulation by the acyl carrier protein
	Sztain T.; Bartholow T.G.; Lee D.J.; Casalino L.; Mitchell A.; Young M.A.; Wang J.; McCammon J.A.; Burkart M.D.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Płoskon et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acyl carrier protein; Chain flipping; Molecular dynamics; Nuclear magnetic resonance
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/179854
作者单位	Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093-0358, United States; Department of Pharmacology, University of California San Diego, San Diego, CA 92093-0340, United States
推荐引用方式 GB/T 7714	Sztain T.,Bartholow T.G.,Lee D.J.,et al. Decoding allosteric regulation by the acyl carrier protein[J],2021,118(16).
APA	Sztain T..,Bartholow T.G..,Lee D.J..,Casalino L..,Mitchell A..,...&Burkart M.D..(2021).Decoding allosteric regulation by the acyl carrier protein.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Sztain T.,et al."Decoding allosteric regulation by the acyl carrier protein".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).