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

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(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
HMB-PP.svg
HMBPP-3D-balls.png
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
PubChem CID
  • 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+ Yes check.svgY
    Key: MDSIZRKJVDMQOQ-GORDUTHDSA-N Yes check.svgY
  • 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).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

(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]

Related Research Articles

Juvenile hormones (JHs) are a group of acyclic sesquiterpenoids that regulate many aspects of insect physiology. The first discovery of a JH was by Vincent Wigglesworth. JHs regulate development, reproduction, diapause, and polyphenisms.The chemical formula for juvenile hormone is .

<span class="mw-page-title-main">Mevalonate pathway</span>

The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K, coenzyme Q10, and all steroid hormones.

<span class="mw-page-title-main">Dimethylallyl pyrophosphate</span> Chemical compound

Dimethylallyl pyrophosphate is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynthesis. It is an isomer of isopentenyl pyrophosphate (IPP) and exists in virtually all life forms. The enzyme isopentenyl pyrophosphate isomerase catalyzes isomerization between DMAPP and IPP.

<span class="mw-page-title-main">Isopentenyl pyrophosphate</span> Chemical compound

Isopentenyl pyrophosphate is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway and in the non-mevalonate MEP pathway of isoprenoid precursor biosynthesis. Isoprenoid precursors such as IPP, and its isomer DMAPP, are used by organisms in the biosynthesis of terpenes and terpenoids.

<span class="mw-page-title-main">HMG-CoA</span> Chemical compound

β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery.

The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The currently preferred name for this pathway is the MEP pathway, since MEP is the first committed metabolite on the route to IPP.

Non-peptidic antigens are low-molecular-weight compounds that stimulate human Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate (IPP) 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.

<span class="mw-page-title-main">Isopentenyl-diphosphate delta isomerase</span> Class of enzymes

Isopentenyl pyrophosphate isomerase, also known as Isopentenyl-diphosphate delta isomerase, is an isomerase that catalyzes the conversion of the relatively un-reactive isopentenyl pyrophosphate (IPP) to the more-reactive electrophile dimethylallyl pyrophosphate (DMAPP). This isomerization is a key step in the biosynthesis of isoprenoids through the mevalonate pathway and the MEP pathway.

<span class="mw-page-title-main">DXP reductoisomerase</span>

DXP reductoisomerase is an enzyme that interconverts 1-deoxy-D-xylulose 5-phosphate (DXP) and 2-C-methyl-D-erythritol 4-phosphate (MEP).

2-<i>C</i>-Methylerythritol 4-phosphate Chemical compound

2-C-Methyl-D-erythritol 4-phosphate (MEP) is an intermediate on the MEP pathway of isoprenoid precursor biosynthesis. It is the first committed metabolite on that pathway on the route to IPP and DMAPP.

In enzymology, a 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (HMB-PP synthase, IspG, EC 1.17.7.1) is an enzyme that catalyzes the chemical reaction

2-C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase is a zinc-dependent enzyme and a member of the YgbB N terminal protein domain, which participates in the MEP pathway of isoprenoid precursor biosynthesis. It catalyzes the following reaction:

<span class="mw-page-title-main">Diphosphomevalonate decarboxylase</span> InterPro Family

Diphosphomevalonate decarboxylase (EC 4.1.1.33), most commonly referred to in scientific literature as mevalonate diphosphate decarboxylase, is an enzyme that catalyzes the chemical reaction

In enzymology, a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase is an enzyme that catalyzes the chemical reaction

Gamma delta T cells are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).

2-C-Methyl-<small>D</small>-erythritol-2,4-cyclopyrophosphate Chemical compound

2-C-Methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) is an intermediate in the MEP pathway (non-mevalonate) of isoprenoid precursor biosynthesis. MEcPP is produced by MEcPP synthase (IspF) and is a substrate for HMB-PP synthase (IspG).

4-Diphosphocytidyl-2-C-methylerythritol is an intermediate in the MEP pathway of isoprenoid precursor biosynthesis. It is produced by the enzyme 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) and is a substrate for CDP-ME kinase (IspE).

4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (EC 1.17.1.2, isopentenyl-diphosphate:NADP+ oxidoreductase, LytB, (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase, HMBPP reductase, IspH, LytB/IspH) is an enzyme in the non-mevalonate pathway. It acts upon (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (or "HMB-PP").

<span class="mw-page-title-main">YgbB N terminal protein domain</span>

In molecular biology, YgbB is a protein domain. This entry makes reference to a number of proteins from eukaryotes and prokaryotes which share this common N-terminal signature and appear to be involved in terpenoid biosynthesis. The YgbB protein is a putative enzyme thought to aid terpenoid and isoprenoid biosynthesis, a vital chemical in all living organisms. This protein domain is part of an enzyme which catalyses a reaction in a complex pathway.

Michel Rohmer, born on 31 January 1948, is a French chemist specialising in the chemistry of micro-organisms. He has particularly studied isoprenoids.

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. 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.