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Noncanonical Radical SAM Enzyme Chemistry Learned from Diphthamide Biosynthesis

Noncanonical Radical SAM Enzyme Chemistry Learned from Diphthamide Biosynthesis

Authors :
Hening Lin
Yugang Zhang
Min Dong
Source :
Biochemistry. 57:3454-3459
Publication Year :
2018
Publisher :
American Chemical Society (ACS), 2018.

Abstract

Radical S-adenosylmethionine (SAM) enzymes are a superfamily of enzymes that use SAM and reduced [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical to catalyze numerous challenging reactions. We have reported a type of noncanonical radical SAM enzymes in the diphthamide biosynthesis pathway. These enzymes also use SAM and reduced [4Fe-4S] clusters, but generate a 3-amino-3-carboxypropyl (ACP) radical to modify the substrate protein, translation elongation factor 2. The regioselective cleavage of a different C-S bond of the sulfonium center of SAM in these enzymes comparing to canonical radical SAM enzymes is intriguing. Here, we highlight some recent findings in the mechanism of these types of enzymes, showing that the diphthamide biosynthetic radial SAM enzymes bound SAM with a distinct geometry. In this way, the unique iron of the [4Fe-4S] cluster in the enzyme can only attack the carbon on the ACP group to form an organometallic intermediate. The homolysis of the organometallic intermediate releases the ACP radical and generates the EF2 radial.

Details

ISSN :
15204995 and 00062960
Volume :
57
Database :
OpenAIRE
Journal :
Biochemistry
Accession number :
edsair.doi.dedup.....1b8fdefd741293dc20bb1e836717cf8e
Full Text :
https://doi.org/10.1021/acs.biochem.8b00287