TY - JOUR
T1 - Mechanistic diversity of radical S-adenosylmethionine (SAM)-dependent methylation
AU - Bauerle, Matthew R.
AU - Schwalm, Erica L.
AU - Booker, Squire J.
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
PY - 2015/2/13
Y1 - 2015/2/13
N2 - Radical S-adenosylmethionine (SAM) enzymes use the oxidizing power of a 5′-deoxyadenosyl 5′-radical to initiate an amazing array of transformations, usually through the abstraction of a target substrate hydrogen atom. A common reaction of radicalSAM(RS) enzymes is the methylation of unactivated carbon or phosphorous atoms found in numerous primary and secondary metabolites, as well as in proteins, sugars, lipids, and RNA. However, neither the chemical mechanisms by which these unactivated atoms obtain methyl groups nor the actual methyl donors are conserved. In fact, RS methylases have been grouped into three classes based on protein architecture, cofactor requirement, and predicted mechanism of catalysis. Class A methylases use two cysteine residues to methylate sp2-hybridized carbon centers. Class B methylases require a cobalamin cofactor to methylate both sp2-hybridized and sp3-hybridized carbon centers as well as phosphinate phosphorous atoms. Class C methylases share significant sequence homology with the RS enzyme, HemN, and may bind two SAM molecules simultaneously to methylate sp2-hybridized carbon centers. Lastly, we describe a new class of recently discovered RS methylases. These ClassDmethylases, unlike Class A, B, and C enzymes, which use SAM as the source of the donated methyl carbon, are proposed to methylate sp2-hybridized carbon centers using methylenetetrahydrofolate as the source of the appended methyl carbon.
AB - Radical S-adenosylmethionine (SAM) enzymes use the oxidizing power of a 5′-deoxyadenosyl 5′-radical to initiate an amazing array of transformations, usually through the abstraction of a target substrate hydrogen atom. A common reaction of radicalSAM(RS) enzymes is the methylation of unactivated carbon or phosphorous atoms found in numerous primary and secondary metabolites, as well as in proteins, sugars, lipids, and RNA. However, neither the chemical mechanisms by which these unactivated atoms obtain methyl groups nor the actual methyl donors are conserved. In fact, RS methylases have been grouped into three classes based on protein architecture, cofactor requirement, and predicted mechanism of catalysis. Class A methylases use two cysteine residues to methylate sp2-hybridized carbon centers. Class B methylases require a cobalamin cofactor to methylate both sp2-hybridized and sp3-hybridized carbon centers as well as phosphinate phosphorous atoms. Class C methylases share significant sequence homology with the RS enzyme, HemN, and may bind two SAM molecules simultaneously to methylate sp2-hybridized carbon centers. Lastly, we describe a new class of recently discovered RS methylases. These ClassDmethylases, unlike Class A, B, and C enzymes, which use SAM as the source of the donated methyl carbon, are proposed to methylate sp2-hybridized carbon centers using methylenetetrahydrofolate as the source of the appended methyl carbon.
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U2 - 10.1074/jbc.R114.607044
DO - 10.1074/jbc.R114.607044
M3 - Review article
C2 - 25477520
AN - SCOPUS:84922879470
SN - 0021-9258
VL - 290
SP - 3995
EP - 4002
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -