AI Article Synopsis
- A class of reactions involving S-adenosylmethionine (AdoMet) has been identified where it initiates free radical formation through a specific radical intermediate called the 5'-deoxyadenosyl radical.
- The reactions are compared with those that depend on adenosylcobalamin, highlighting that while the radical precursor formation mechanisms differ, their functions of hydrogen abstraction from substrates are similar.
- The paper will discuss how AdoMet is converted to the 5'-deoxyadenosyl radical in enzyme reactions and will compare its role in different enzymatic processes.
Article Abstract
A class of enzymatic reactions of S-adenosylmethionine (AdoMet) has recently been recognized, in which AdoMet plays a novel role by initiating free radical formation through the intermediate formation of 5'-deoxyadenosine-5'-yl, the 5'-deoxyadenosyl radical. The reactions are in this way related to adenosylcobalamin-dependent processes, which also depend on the formation of the 5'-deoxyadenosyl radical as an intermediate. The mechanisms by which the 5'-deoxyadenosyl radical is generated by the AdoMet- and adenosylcobalamin-dependent enzymes are very different. However, the functions of the 5'-deoxyadenosyl radical are similar in that in all cases it abstracts hydrogen from a substrate to form 5'-deoxyadenosine and a substrate-derived free radical. In this paper, the role of the 5'-deoxyadenosyl radical in the reaction of the adenosylcobalamin-dependent reactions will be compared with its role in the AdoMet-dependent reaction of lysine 2,3-aminomutase. The mechanism by which AdoMet is cleaved to the 5'-deoxyadenosyl radical at enzymatic sites will also be discussed.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/abbi.2000.2010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Radical-Mediated Nucleophilic Peptide Cross-Linking in Dynobactin Biosynthesis.
J Am Chem Soc
November 2024
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina 27710, United States.
Dynobactins are recently discovered ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotics that selectively kill Gram-negative pathogens by inhibiting the β-barrel assembly machinery (Bam) located on their outer membranes. Such activity of dynobactins derives from their unique cross-links between Trp1-Asn4 and His6-Tyr8. In particular, the His6-Tyr8 cross-link is formed between N of His6 and C of Tyr8, an unprecedented type of cross-link in RiPP natural products.
View Article and Find Full Text PDFRadicals are highly reactive, short-lived chemical species that normally react indiscriminately with biological materials, and yet, nature has evolved thousands of enzymes that employ radicals to catalyze thermodynamically challenging chemistry. How these enzymes harness highly reactive radical intermediates to steer the catalysis to the correct outcome is a topic of intense investigation. Here, the results of detailed QM/MM calculations on archetype radical B-enzymes are presented that provide new insights into how these enzymes control the reactivity of radicals within their active sites.
View Article and Find Full Text PDFArsinothricin Biosynthesis Involving a Radical SAM Enzyme for Noncanonical SAM Cleavage and C-As Bond Formation.
J Am Chem Soc
August 2024
Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Arsinothricin is a potent antibiotic secreted by soil bacteria. The biosynthesis of arsinothricin was proposed to involve a C-As bond formation between trivalent As and the 3-amino-3-carboxypropyl (ACP) group of -adenosyl-l-methionine (SAM), which is catalyzed by the protein ArsL. However, ArsL has not been characterized in detail.
View Article and Find Full Text PDFElucidation of factors shaping reactivity of 5'-deoxyadenosyl - a prominent organic radical in biology.
Phys Chem Chem Phys
July 2024
J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Dolejškova 3, 18200 Prague, Czech Republic.
This study investigates the factors modulating the reactivity of 5'-deoxyadenosyl (5'dAdo˙) radical, a potent hydrogen atom abstractor that forms in the active sites of radical SAM enzymes and that otherwise undergoes a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5'dAdo˙ in aqueous solution and in two enzymatic microenvironments. With that we reveal that HAA efficiency of 5'dAdo˙ is due to (i) the formation of 5'dAdo˙ in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5'dAdo˙ complex formation, and (ii) the prevention of the conformational changes associated with self-decay by a tight active-site cavity.
View Article and Find Full Text PDFRadical -Adenosyl-l-Methionine Enzyme PylB: A C-Centered Radical to Convert l-Lysine into (3)-3-Methyl-d-Ornithine.
J Am Chem Soc
March 2024
Univ. Grenoble Alpes, CEA, CNRS, IBS, Metalloproteins Unit, F-38000 Grenoble, France.
PylB is a radical -adenosyl-l-methionine (SAM) enzyme predicted to convert l-lysine into (3)-3-methyl-d-ornithine, a precursor in the biosynthesis of the 22nd proteogenic amino acid pyrrolysine. This protein highly resembles that of the radical SAM tyrosine and tryptophan lyases, which activate their substrate by abstracting a H atom from the amino-nitrogen position. Here, combining assays, analytical methods, electron paramagnetic resonance spectroscopy, and theoretical methods, we demonstrated that instead, PylB activates its substrate by abstracting a H atom from the Cγ position of l-lysine to afford the radical-based β-scission.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!