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

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate HMB-PP.svg 190px Chemical structure of HMB-PP HMBPP-3D-balls.png 240px Ball-and-stick model, shown here as a 3- ion (2E)-4-Hydroxy-3-methylbut-2-en-1-yl trihydrogen diphosphate (E)-4-hydroxy-dimethylallyl pyrophosphateHDMAPP(E)-4-Hydroxy-3-methyl-but-2-enyl diphosphateHMBDP 396726-03-7 correct CAS correct chemspider correct EBI 15664 4445244 O=P(O)(O)OP(=O)(O)OCC=C(C)CO correct chemspider 1S/C5H12O8P2/c1-5(4-6)2-3-12-15(10,11)13-14(7,8)9/h2,6H,3-4H2,1H3,(H,10,11)(H2,7,8,9)/b5-2+ correct chemspider MDSIZRKJVDMQOQ-GORDUTHDSA-N correct EBI 145233 5281976 C11811 5 12 8 2 (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis. Rohmer M The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants Natural Product Reports 16 5 565–74 1999 10584331 10.1039/a709175c Rohmer Michel Fox DT Poulter CD Synthesis of (E)-4-hydroxydimethylallyl diphosphate. An intermediate in the methyl erythritol phosphate branch of the isoprenoid pathway The Journal of Organic Chemistry 67 14 5009–10 2002 12098326 10.1021/jo0258453 The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH). Biochemical role Non-mevalonate pathway HMB-PP is an intermediate in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate. Eisenreich W Bacher A Arigoni D Rohdich F Biosynthesis of isoprenoids via the non-mevalonate pathway Cellular and Molecular Life Sciences 61 12 1401–26 2004 15197467 10.1007/s00018-004-3381-z 24558920 11138651 Hunter, WN 2007 The Non-mevalonate Pathway of Isoprenoid Precursor Biosynthesis Journal of Biological Chemistry 282 30 21573–21577 10.1074/jbc.R700005200 17442674 free Most gram-negative bacteria, the photosynthetic cyanobacteria and green algae use only this pathway, while higher plants also use the mevalonate pathway.Vranová Eva Coman Diana Gruissem Wilhelm 2013-04-29 Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis https://www.annualreviews.org/doi/10.1146/annurev-arplant-050312-120116 Annual Review of Plant Biology en 64 1 665–700 10.1146/annurev-arplant-050312-120116 23451776 2013AnRPB..64..665V 1543-5008 subscription The enzyme 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase uses two reduced ferredoxin proteins per molecule of the precursor MEcPP to convert it to HMB-PP:Hecht Stefan Eisenreich Wolfgang Adam Petra Amslinger Sabine Kis Klaus Bacher Adelbert Arigoni Duilio Rohdich Felix Studies on the nonmevalonate pathway to terpenes: The role of the GcpE (IspG) protein Proceedings of the National Academy of Sciences 2001 98 26 14837–14842 10.1073/pnas.201399298 free 11752431 64945 Okada Ken Hase Toshiharu Cyanobacterial Non-mevalonate Pathway Journal of Biological Chemistry 2005 280 21 20672–20679 10.1074/jbc.M500865200 free 15792953 70% Q27103069 MEcPP + 2 oxidised ferredoxin H2O Q76285996 HMB-PP + 2 reduced ferredoxin The final step in the non-mevalonate pathway is carried out by the enzyme 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, which gives a mixture of dimethylallyl pyrophosphate and isopentenyl pyrophosphate in the ratio of five to one. On the reduction steps in the mevalonate independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in the bacterium Zymomonas mobilis Charon, L. Pale-Grosdemange, C. Rohmer, M. Tetrahedron Lett. 1999 40 40 7231–7234 10.1016/s0040-4039(99)01531-2 Röhrich RC, Englert N, Troschke K, Reichenberg A, Hintz M, Seeber F, Balconi E, Aliverti A, Zanetti G, Köhler U, Pfeiffer M, Beck E, Jomaa H, Wiesner J Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum FEBS Letters 579 28 6433–8 November 2005 16289098 10.1016/j.febslet.2005.10.037 free 60% HMB-PP +2 reduced ferredoxin 2 H+ H2O dimethylallyl pyrophosphate + 2 oxidised ferredoxin 60% HMB-PP +2 reduced ferredoxin 2 H+ H2O isopentenyl pyrophosphate + 2 oxidised ferredoxin The products are then used in terpenoid biosynthesis. 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 ("phosphoantigen") 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. Activation of human γδ T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor Periplakin Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J 2015 J Immunol 10.4049/jimmunol.1401064 25637025 4337483 194 5 2390–8 References External links 4-hydroxy-3-methylbut-2-enyl+pyrophosphate Category:Biomolecules Category:Metabolism Category:Pyrophosphate esters Category:Hemiterpenes