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Mechanisms of Radical SAM Enzymes Probed by EPR Spectroscopy

EPR 光谱探讨自由基 SAM 酶的作用机制

基本信息

批准号：
8632910
负责人：
R David Britt
金额：
$ 31.59万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8632910
关键词：
9-mercaptodethiobiotin Active Sites Affect Anabolism Antibiotics Anticodon Arizona Berlin Binding Biochemical Biological Biology Biotin Chemicals Chemistry Cleaved cell Codon Nucleotides Complex DNA Sequence Rearrangement Data Set Divalent Cations Electron Nuclear Double Resonance Electron Spin Resonance Spectroscopy Electronics Electrons Environment Enzymes Equipment Event Excision Family Felis catus Funding Goals Guanine Hawaii Health Human Hydrogen Hydrogenase Ions Isotope Labeling Kinetics Label Laboratories Learning Ligands Light Lyase Magnetic Resonance Magnetism Mass Spectrum Analysis Measures Metals Methods Modeling Modification Nature Nitrogen Nucleoside Q Oxygen Pathway interactions Play Positioning Attribute Preparation Property Protein Biosynthesis Proteins Protons RNA Radioisotopes Reaction Rest S-Adenosylmethionine Sampling Sequence Analysis Side Site Spectroscopy, Fourier Transform Infrared Spectrum Analysis Structure Sulfur Time Transfer RNA Tyrosine United States National Institutes of Health Universities Vitamins Work base biotin synthase chemical reaction design desthiobiotin divalent metal electronic structure enzyme activity geometric structure improved instrument interest iron hydrogenase public health relevance research study tetrahydropterin thiophane vitamin biosynthesis

项目摘要

Project Summary Nature uses highly reactive radicals to carry out a diverse set of biochemical functions, many of which are essen- tial to maintaining proper human health. These potent biological radical reactions need to be carried out safely, producing essential specific products, without dangerous side reactions occurring. A large number of such rad- ical reactions are performed by the family of radical SAM enzymes, which use a [4Fe-4S] center with a bound S-adenosylmethionine (SAM) molecule to generate a strongly oxidizing 5'-deoxyadenosyl radical which can in turn drive a large number of difficult chemical reactions. We will target mechanistic aspects of several classes of radical SAM enzymes. Biotin synthase is a radical SAM enzyme that catalyzes the final step in the biosynthesis of the vitamin biotin. A set of Fe-S and radical SAM maturase enzymes are used to build the unique Fe-S center of Fe-Fe hydrogenase, an enzyme which catalyzes the important reduction of protons to dihydrogen and vice versa. And radical SAM enzymes are used to modify many bases in transfer RNA, improving codon-anticodon recognition in order to make protein synthesis more reliable. We are specifically interested in a radical SAM enzyme QueE that is essential for generating 7-deazapurines. This proposal describes a magnetic resonance spectroscopic approach to study such diverse radical SAM enzymes. Specifically, we are using electron para- magnetic resonance (EPR) spectroscopy, which can precisely measure the magnetic environment of unpaired electrons in the radical SAM Fe-S clusters, in the organic radicals that these clusters generate, and in secondary metal centers that are involved in the reactions in many of these enzymes.

项目总结