(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
3D model (JSmol)	Interactive image; Interactive image;
ChEBI	CHEBI:15664 ;
ChEMBL	ChEMBL145233 ;
ChemSpider	4445244 ;
PubChem CID	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	262.091 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

(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

^ 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. 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. PMC 4337483. PMID 25637025.

External links

4-hydroxy-3-methylbut-2-enyl+pyrophosphate at the US National Library of Medicine Medical 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. 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.

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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)	Interactive image Interactive image
ChEBI	CHEBI:15664
ChEMBL	ChEMBL145233
ChemSpider	4445244
PubChem CID	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	262.091 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).