Glucose-1-phosphate thymidylyltransferase (RmlA)

Glucose-1-phosphate thymidylyltransferase, also known as RmlA, is a nucleotidyltransferase enzyme (EC 2.7.7.24) that catalyzes the condensation of dTTP and α-D-glucose 1-phosphate to form dTDP-glucose and pyrophosphate[2][3][6]. This reaction is the committed first step in the biosynthetic pathway for dTDP-L-rhamnose, an essential sugar in the cell wall of many pathogenic bacteria such as Pseudomonas aeruginosa and Mycobacterium tuberculosis[4][5][7]. By enabling L-rhamnose synthesis, RmlA supports the assembly of vital bacterial cell wall glycoconjugates; its function is absent in mammals, making RmlA a promising antibacterial drug target[1][4][5][7]. Structurally, RmlA is typically a homotetramer with specialized allosteric regulation[4][5]. Inhibitors targeting RmlA disrupt bacterial cell wall formation and are under active investigation for novel antibacterial therapies[5][7].

Other names

dTDP-glucose diphosphorylasedTDP-glucose pyrophosphorylasedTDP-glucose synthaseGptT (especially in plants)

Competitive inhibition (including allosteric inhibition that prevents substrate-induced conformational changes); Prevention of nucleotide-sugar formation required for bacterial cell wall synthesis