Structural and functional insight into serine hydroxymethyltransferase from <i>Helicobacter pylori</i> - Fig 1

Thymidylate synthesis cycles involving thymidylate synthase ThyA (A) or thymidylate synthase ThyX (B). Both enzymes, ThyA and ThyX, perform de novo synthesis of deoxythymidine monophosphate (dTMP; thymidylate) from deoxyuridine monophosphate (dUMP). ThyA proteins use methylenetetrahydrofolate (MTHF) both as carbon and electron source, resulting in the formation of dihydrofolate (DHF), which is subsequently reduced by dihydrofolate reductase (DHFR). The ThyX flavoenzymes produce tetrahydrofolate (THF) as reaction product and not dihydrofolate; consequently DHFR is absent. This key difference in ThyA and ThyX catalysis has important implications for the bacterial folate metabolism. The third key enzyme implicated in generation of MTHF, serine hydroxymethyltransferase (SHMT), has a universal phylogenetic distribution.