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

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
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
CAS Number	396726-03-7[ChemSpider];
3D model (JSmol)	Interactive image; Interactive image;
ChEBI	CHEBI:15664;
ChEMBL	ChEMBL145233;
ChemSpider	4445244;
PubChemCID	21597501;
	InChI 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+ Key: MDSIZRKJVDMQOQ-GORDUTHDSA-N; 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;
	SMILES CC(=CCOP(=O)([O-])OP(=O)([O-])[O-])CO; O=P(OP(=O)(O)O)(OC/C=C(/CO)C)O;
Properties
Chemical formula	C5H12O8P2
Molar mass	262.091g·mol−1
	Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa). verify(what is?) Infobox references

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate(HMBPPorHMB-PP) is an intermediate of theMEP pathway(non-mevalonate pathway) of isoprenoid biosynthesis.^[1]^[2]The enzymeHMB-PP synthase(GcpE, IspG) catalyzes the conversion of2-C-methyl-D-erythritol 2,4-cyclodiphosphate(MEcPP) into HMB-PP. HMB-PP is then converted further toisopentenyl pyrophosphate(IPP) anddimethylallyl pyrophosphate(DMAPP) byHMB-PP reductase(LytB, IspH).

HMB-PP is an essential metabolite in most pathogenic bacteria includingMycobacterium tuberculosisas well as inmalariaparasites, but is absent from the human host.^[3]

HMB-PP is the physiological activator ( "phosphoantigen") for humanVγ9/Vδ2 T cells,the majorγδ T cellpopulation 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 asIPP or alkyl amines.HMB-PP functions in this capacity by binding the B30.2 domain ofBTN3A1.^[4]

References

^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.
^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.
^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.PMC11138651.PMID 15197467.S2CID 24558920.
^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.PMC4337483.PMID 25637025.

External links

4-hydroxy-3-methylbut-2-enyl+pyrophosphateat the U.S. National Library of MedicineMedical Subject Headings(MeSH)

[Rohmer-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.

[Poulter-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.

[Eisenreich-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.PMC11138651.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.PMC4337483.PMID 25637025.

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