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Noncanonical Radical SAM Enzyme Chemistry Learned from Diphthamide Biosynthesis
Noncanonical Radical SAM Enzyme Chemistry Learned from Diphthamide Biosynthesis
- 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.
- Subjects :
- Iron-Sulfur Proteins
0301 basic medicine
chemistry.chemical_classification
S-Adenosylmethionine
biology
Stereochemistry
Sulfonium
Diphthamide
biology.organism_classification
Biochemistry
Article
Biosynthetic Pathways
Substrate Specificity
Homolysis
03 medical and health sciences
chemistry.chemical_compound
Pyrococcus horikoshii
030104 developmental biology
Enzyme
chemistry
Biosynthesis
Histidine
Radical SAM
Subjects
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