An Enzyme Containing the Conserved Domain of Unknown Function DUF62 Acts as a Stereoselective (Rs,Sc)-S-Adenosylmethionine Hydrolase |
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Authors: | Taylor Kornfuehrer Sean Romanowski Prof Dr Valérie de Crécy-Lagard Prof Dr Andrew D Hanson Prof Dr Alessandra S Eustáquio |
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Affiliation: | 1. Department of Pharmaceutical Sciences and, Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607 USA;2. Department of Microbiology and Cell Science and, Genetics Institute, University of Florida, Gainesville, FL 32611 USA;3. Horticultural Sciences Department, University of Florida, Gainesville, FL 32611 USA |
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Abstract: | Homochirality is a signature of biological systems. The essential and ubiquitous cofactor S-adenosyl-l -methionine (SAM) is synthesized in cells from adenosine triphosphate and l -methionine to yield exclusively the (S,S)-SAM diastereomer. (S,S)-SAM plays a crucial role as the primary methyl donor in transmethylation reactions important to the development and homeostasis of all organisms from bacteria to humans. However, (S,S)-SAM slowly racemizes at the sulfonium center to yield the inactive (R,S)-SAM, which can inhibit methyltransferases. Control of SAM homochirality has been shown to involve homocysteine S-methyltransferases in plants, insects, worms, yeast, and in ∼18 % of bacteria. Herein, we show that a recombinant protein containing a domain of unknown function (DUF62) from the actinomycete bacterium Salinispora tropica functions as a stereoselective (R,S)-SAM hydrolase (adenosine-forming). DUF62 proteins are encoded in the genomes of 21 % of bacteria and 42 % of archaea and potentially represent a novel mechanism to remediate SAM damage. |
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Keywords: | AdoMet hydrolase methyltransferase S-adenosylmethionine S-adenosyl-l-methionine SAM |
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