Simon Arragain
Biological radical sulfur insertion. A study of methylthiotransferases
Published on 7 October 2011
Body text 1
Thesis presented October 07, 2011
Abstract:
One of the chemically most challenging problems in enzymology is the functionalization of non-reactive C–H bonds. Such reactions require specialized cofactors as heme, Fe-µ-oxo or vitamin B12. In 2001, special Fe-S centers able to bind S-Adenosylmethionine (SAM) have been shown to activate non-reactive C-H bonds toward subsequent functionalization. Enzymes containing this new cofactor constitute a super-family called “Radical SAM”. Methylthiotransferases (MTTases) belong to the “Radical SAM” super-family and catalyze the insertion of a methylthio group (-SCH3) in C-H bonds. By doing
in vitro and
in vivo experiments, we were able to classify them into three groups. The first class, (RimO) catalyzes the formation of
ß-methylthio-aspartate
89 on the ribosomal protein
S12 (ß-ms-D89-S12) whereas the two others (MiaB and MtaB/eMtaB) respectively catalyse the thiomethylation of the nucleosides
2-methylthio-N6-isopentenyladenosine 37 (ms2i6A-37) and
2-methylthio-N6-threoninecarbamoyl
adenosine
37 (ms2t6A-37) present in some tRNA. Our studies have shown that,
in vitro, MTTases catalyze the insertion of a SCH3 group in a catalytic way suggesting entirely new radical sulfur insertion mechanisms.
Keywords:
Methylthiotransferases, RimO, MiaB, Radical SAM, MtaB, CDKAL1
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