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

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
Chemical structure of HMB-PP
Ball-and-stick model, shown here as a 3- ion
Names
IUPAC name
(E)-4-hydroxy-3-methylbut-2-enoxy-oxidophosphoryl phosphate
Other names
(E)-4-hydroxy-dimethylallyl pyrophosphate
HDMAPP
(E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate
HMBDP
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
  • InChI=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+ checkY
    Key: MDSIZRKJVDMQOQ-GORDUTHDSA-N checkY
  • InChI=1/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+
    Key: MDSIZRKJVDMQOQ-GORDUTHDBB
  • CC(=CCOP(=O)([O-])OP(=O)([O-])[O-])CO
  • O=P(OP(=O)(O)O)(OC/C=C(/CO)C)O
Properties
C5H12O8P2
Molar mass 262.091 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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(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.[1][2] 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).

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.[3]

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.[4]

References

  1. ^ Rohmer, M; Rohmer, Michel (1999). "The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants". Natural Product Reports. 16 (5): 565–74. doi:10.1039/a709175c. PMID 10584331.
  2. ^ Fox, DT; Poulter, CD (2002). "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. doi:10.1021/jo0258453. PMID 12098326.
  3. ^ Eisenreich, W; Bacher, A; Arigoni, D; Rohdich, F (2004). "Biosynthesis of isoprenoids via the non-mevalonate pathway". Cellular and Molecular Life Sciences. 61 (12): 1401–26. doi:10.1007/s00018-004-3381-z. PMC 11138651. PMID 15197467. S2CID 24558920.
  4. ^ Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J (2015). "Activation of human γδ T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor Periplakin". J Immunol. 194 (5): 2390–8. doi:10.4049/jimmunol.1401064. PMC 4337483. PMID 25637025.