Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli.
The gcpE and lytB gene products control the terminal steps of isoprenoid biosynthesis via the 2-C-methyl-D-erythritol 4-phosphate pathway in Escherichia coli. In lytB-deficient mutants, a highly immunogenic compound accumulates significantly, compared to wild-type E. coli, but is apparently absent in gcpE-deficient mutants. Here, this compound was purified from E. coli DeltalytB mutants by preparative anion exchange chromatography, and identified by mass spectrometry, (1)H, (13)C and (31)P NMR spectroscopy, and NOESY analysis as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). HMB-PP is 10(4) times more potent in activating human Vgamma9/Vdelta2 T cells than isopentenyl pyrophosphate.
Hintz
M
M
Jomaa Pharmaka GmbH, Frankfurter Strasse 50, 35392 Giessen, Germany. martin.hintz@jomaa.de
Reichenberg
A
A
Altincicek
B
B
Bahr
U
U
Gschwind
R M
RM
Kollas
A K
AK
Beck
E
E
Wiesner
J
J
Eberl
M
M
Jomaa
H
H
D001426:Bacterial Proteins / Q000235:genetics; D011756:Diphosphates / Q000737:chemistry / Q000494:pharmacology*; D004798:Enzymes; D004896:Erythritol / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological; D019906:Nuclear Magnetic Resonance, Biomolecular; D010088:Oxidoreductases; D016692:Receptors, Antigen, T-Cell, gamma-delta; D021241:Spectrometry, Mass, Electrospray Ionization; D013403:Sugar Phosphates / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D013729:Terpenes / Q000378:metabolism
C114232:2-C-methylerythritol 4-phosphate; C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D001426:Bacterial Proteins; D011756:Diphosphates; D004798:Enzymes; D029968:Escherichia coli Proteins; D008934:Mitogens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013403:Sugar Phosphates; D013729:Terpenes; C421242:hydroxymethylbutenyl 4-diphosphate synthase; D010088:Oxidoreductases; C109866:ispH protein, E coli; D004896:Erythritol