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Mechanism of Radical Initiation in the Radical SAM Enzyme Superfamily

Journal Article · · Annual Review of Biochemistry
 [1];  [2];  [2]
  1. Northwestern Univ., Evanston, IL (United States); OSTI
  2. Montana State Univ., Bozeman, MT (United States)
+ Show Author Affiliations
Radical S-adenosylmethionine (SAM) enzymes use a site-differentiated [4Fe-4S] cluster and SAM to initiate radical reactions through liberation of the 5'-deoxyadenosyl (5'-dAdo•) radical. They form the largest enzyme superfamily, with more than 700,000 unique sequences currently, and their numbers continue to grow as a result of ongoing bioinformatics efforts. The range of extremely diverse, highly regio- and stereo-specific reactions known to be catalyzed by radical SAM superfamily members is remarkable. The common mechanism of radical initiation in the radical SAM superfamily is the focus of this review. Most surprising is the presence of an organometallic intermediate, Ω, exhibiting an Fe–C5'-adenosyl bond. Regioselective reductive cleavage of the SAM S–C5' bond produces 5'-dAdo• to form Ω, with the regioselectivity originating in the Jahn–Teller effect. Ω liberates the free 5'-dAdo• as the catalytically active intermediate through homolysis of the Fe–C5' bond, in analogy to Co–C5' bond homolysis in B12, which was once viewed as biology's choice of radical generator.
Research Organization:
Montana State Univ., Bozeman, MT (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC)
Grant/Contract Number:
SC0005404
OSTI ID:
2419699
Journal Information:
Annual Review of Biochemistry, Journal Name: Annual Review of Biochemistry Journal Issue: 1 Vol. 92; ISSN 0066-4154
Publisher:
Annual ReviewsCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
5'-deoxyadenosyl radical
59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
S-adenosylmethionine
organometallic
radical SAM