Enzyme catalyzed formation of radicals from S-adenosylmethionine and inhibition of enzyme activity by the cleavage products
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- 作者：Martyn J. Hiscox ; Rebecca C. Driesener ; Peter L. Roach
- 关键词：SAM ; S-adenosylmethionine ; DOA&bull ; 5&prime ; -deoxyadenosine radical ; MTA ; 5&prime ; -methylthioadenosine ; ACP&bull ; 3-amino-3-carboxypropyl radical ; GRE ; glycyl radical enzyme ; XAS ; X-ray absorption spectroscopy ; PLP ; 5&prime ; -pyridoxal phosphate ; DTB ; d
- 刊名：Biochimica et Biophysica Acta - Proteins and Proteomics
- 出版年：2012
- 出版时间：November, 2012
- 年：2012
- 卷：1824
- 期：11
- 页码：1165-1177
- 全文大小：1693 K
文摘
A large superfamily of enzymes have been identified that make use of radical intermediates derived by reductive cleavage of S-adenosylmethionine. The primary nature of the radical intermediates makes them highly reactive and potent oxidants. They are used to initiate biotransformations by hydrogen atom abstraction, a process that allows a particularly diverse range of substrates to be functionalized, including substrates with relatively inert chemical structures. In the first part of this review, we discuss the evidence supporting the mechanism of radical formation from S-adenosylmethionine. In the second part of the review, we examine the potential of reaction products arising from S-adenosylmethionine to cause product inhibition. The effects of this product inhibition on kinetic studies of ¡®radical S-adenosylmethionine¡¯ enzymes are discussed and strategies to overcome these issues are reviewed. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.