Article ID Journal Published Year Pages File Type
1178482 Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2012 13 Pages PDF
Abstract

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.

► Alternative SAM cleavage pathways. ► SAM cleavage products and product-like molecules may be inhibitory. ► Product inhibition of radical SAM enzymes can be relieved by MTAN. ► Substrate binding lowers the energetic barrier to radical formation.

Related Topics
Physical Sciences and Engineering Chemistry Analytical Chemistry
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