Thymidine monophosphate kinase (Mycobacterium tuberculosis) (TMPKmt)

Thymidine monophosphate kinase (TMPKmt) is an essential enzyme in Mycobacterium tuberculosis, encoded by the tmk gene (Rv3247c)[1][6]. It catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), a critical step in the de novo and salvage pathways of DNA synthesis and repair[1][5][6]. This enzyme is structurally unique to the bacterium, making it a promising therapeutic target for tuberculosis drug development[2][3]. Inhibiting TMPKmt disrupts nucleotide synthesis, compromising mycobacterial DNA replication and survival, particularly important for non-replicating (dormant) forms of the bacterium[1][2]. Despite promising inhibitors identified in research, challenges remain with intracellular drug delivery and selective inhibition versus the human homologs[2][3].

Other names

thymidylate kinasethymidylic acid kinaseATP:dTMP phosphotransferasetmk (gene name)TMPK (general abbreviation)

Inhibition of TMPKmt depletes dTDP and dTTP pools, thereby blocking DNA synthesis and cell division in M. tuberculosis[1][2][3]