(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate


-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate is an intermediate of the MEP pathway of isoprenoid biosynthesis. The enzyme HMB-PP synthase catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate and dimethylallyl pyrophosphate by HMB-PP reductase.
HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis as well as in malaria parasites, but is absent from the human host.
HMB-PP is the physiological activator for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood. With a bioactivity of 0.1 nM it is 10,000-10,000,000 times more potent than any other natural compound, such as IPP or alkyl amines. HMB-PP functions in this capacity by binding the B30.2 domain of BTN3A1.