Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human γδ T cells in Escherichia coli

被引:296
|
作者
Hintz, M
Reichenberg, A
Altincicek, B
Bahr, U
Gschwind, RM
Kollas, AK
Beck, E
Wiesner, J
Eberl, M
Jomaa, H
机构
[1] Jomaa Pharmaka GMBH, D-35392 Giessen, Germany
[2] Univ Frankfurt, D-60590 Frankfurt, Germany
[3] Univ Marburg, Fachbereich Chem, NMR Abt, D-35043 Marburg, Germany
[4] Univ Giessen, Fachbereich Humanmed, Biochem Inst, D-35392 Giessen, Germany
关键词
gamma delta T cell; 2-C-methyl-D-erythritol 4-phosphate pathway; 4-hydroxy-3-methyl-but-2-enyl pyrophosphate; gcpE; lytB;
D O I
10.1016/S0014-5793(01)03191-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Delta lytB mutants by preparative anion exchange chromatography, and identified by mass spectrometry, H-1, C-13 and P-31 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 V gamma9/V delta2 T cells than isopentenyl pyrophosphate. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:317 / 322
页数:6
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