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DOI	10.1073/pnas.2022379118
	Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases
	Iyer S.R.; Tidemand K.D.; Babicz J.T.; Jr.; Jacobs A.B.; Gee L.B.; Haahr L.T.; Yoda Y.; Kurokuzu M.; Kitao S.; Saito M.; Seto M.; Christensen H.E.M.; Peters G.H.J.; Solomon E.I.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	The pterin-dependent nonheme iron enzymes hydroxylate aromatic amino acids to perform the biosynthesis of neurotransmitters to maintain proper brain function. These enzymes activate oxygen using a pterin cofactor and an aromatic amino acid substrate bound to the FeII active site to form a highly reactive FeIV = O species that initiates substrate oxidation. In this study, using tryptophan hydroxylase, we have kinetically generated a pre-FeIV = O intermediate and characterized its structure as a FeII-peroxy-pterin species using absorption, Mössbauer, resonance Raman, and nuclear resonance vibrational spectroscopies. From parallel characterization of the pterin cofactor and tryptophan substrate-bound ternary FeII active site before the O2 reaction (including magnetic circular dichroism spectroscopy), these studies both experimentally define the mechanism of FeIV = O formation and demonstrate that the carbonyl functional group on the pterin is directly coordinated to the FeII site in both the ternary complex and the peroxo intermediate. Reaction coordinate calculations predict a 14 kcal/mol reduction in the oxygen activation barrier due to the direct binding of the pterin carbonyl to the FeII site, as this interaction provides an orbital pathway for efficient electron transfer from the pterin cofactor to the iron center. This direct coordination of the pterin cofactor enables the biological function of the pterin-dependent hydroxylases and demonstrates a unified mechanism for oxygen activation by the cofactor-dependent nonheme iron enzymes. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cofactor-dependent metalloenzymes; Neurotransmitter biosynthesis; Oxygen activation
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/179901
作者单位	Department of Chemistry, Stanford University, Stanford, CA 94305, United States; Department of Chemistry, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; Japan Synchrotron Radiation Research Institute, Hyogo, 679-5198, Japan; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka, 590-0494, Japan; Bioneer A/S, Hørsholm, 2970, Denmark
推荐引用方式 GB/T 7714	Iyer S.R.,Tidemand K.D.,Babicz J.T.,et al. Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases[J],2021,118(15).
APA	Iyer S.R..,Tidemand K.D..,Babicz J.T..,Jr..,Jacobs A.B..,...&Solomon E.I..(2021).Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Iyer S.R.,et al."Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).