Project 10 Prof. Gunhild Layer
The role of iron-sulfur clusters and S-adenosyl-L-methionine in radical-based C-methylation reactions
Enzymatic methylation reactions employing S-adenosyl-L-methionine (SAM) as the methyl group donor usually proceed via an SN2 mechanism during which a suitable nucleophile attacks the electrophilic methyl group of SAM. The responsible SAM-dependent methyltransferases (MTs) are able to methylate nucleophilic oxygen, nitrogen, sulfur and carbon atoms. However, these conventional SAM-dependent MTs are not suitable for the methylation of electrophilic carbon atoms, which requires radical-based catalysis in most cases. The responsible MT enzymes belong to the family of Radical SAM enzymes, which use the combination of a [4Fe-4S] cluster and SAM as cofactors for the initiation of radical catalysis. Currently, the Radical SAM MTs are grouped into four classes according to their domain architecture, cofactor requirement and postulated catalytic mechanism.
The aim of this project is the characterization of two novel Radical SAM MTs, which are proposed to be responsible for the introduction of two unusual posttranslational amino acid modifications found in methyl-coenzyme M reductase (MCR) of methanogenic archaea: 5-C-(S)-methylarginine and 2-C-(S)-methylglutamine. Both Radical SAM MTs are predicted to use cobalamin as additional cofactor for the methylation reaction.
Contact:
Prof. Gunhild Layer
Institute of Pharmaceutical Sciences
Pharmaceutical Biology and Biotechnology
Stefan-Meier-Str. 19, 79104 Freiburg
Phone: +49 (0) 761 203-8373
Fax: +49 (0) 761 203-8383
email: gunhild.layer@pharmazie.uni-freiburg.de