A shuttle of one-carbon units anchored by polyglutamate
Conversion of one-carbon units generally relies on diffusible carrier molecules in methylotrophs. In a recent PNAS paper, the Vorholt group discovered that methylofuran is tightly bound to the enzyme “formyltransferase/hydrolase complex” and transfers formyl units between two active sites.
Metabolic pathways involving the transfer of one-carbon units are essential for all life. For methylotrophs, such pathways form the basis of their energy and carbon metabolism. In the bacterial oxidation pathway of methanol to CO2, the “formyltransferase/hydrolase complex” (Fhc) is essential. It transfers a formyl group to the coenzyme methylofuran before hydrolyzing it to formate. In a previous study (Hemmann et al., JBC, 2016), the Vorholt group showed that methylofuran consists of a core structure to which a large chain of up to 24 glutamates is attached. By determining the structure of Fhc, Hemmann et al. could now show that this polyglutamate chain is branched and firmly bound to the enzyme. The chain functions as a flexible linker that shuttles formyl groups between the two active sites of Fhc, thus enhancing catalysis. The study additionally highlights structural and functional differences between this bacterial enzyme and homologous archaeal enzymes involved in methanogenesis.
Link to the publication in external pageProceedings of the National Academy of Sciences