Nigericin

Nigericin
Names
Preferred IUPAC name
(2R)-2-[(2R,3S,6R)-6-{[(2S,4R,5R,7R,9R,10R)-2-{(2S,2′R,3′S,5R,5′R)-5′-[(2S,3S,5R,6R)-6-Hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-2,3′-dimethyl[2,2′-bioxolan]-5-yl}-9-methoxy-2,4,10-trimethyl-1,6-dioxaspiro[4.5]decan-7-yl]methyl}-3-methyloxan-2-yl]propanoic acid
Other names
Polyetherin A, Azalomycin M, Helixin C, Helix C
Identifiers
CAS Number
  • 28380-24-7 checkY
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:7569 checkY
ChEMBL
  • ChEMBL405862 checkY
ChemSpider
  • 10196461 checkY
ECHA InfoCard 100.212.814 Edit this at Wikidata
PubChem CID
  • 34230
UNII
  • RRU6GY95IS checkY
CompTox Dashboard (EPA)
  • DTXSID9041079 Edit this at Wikidata
InChI
  • InChI=1S/C40H68O11/c1-21-11-12-28(46-33(21)26(6)36(42)43)17-29-18-30(45-10)27(7)40(48-29)25(5)19-38(9,51-40)32-13-14-37(8,49-32)35-23(3)16-31(47-35)34-22(2)15-24(4)39(44,20-41)50-34/h21-35,41,44H,11-20H2,1-10H3,(H,42,43)/t21-,22-,23-,24+,25+,26+,27+,28+,29+,30+,31+,32+,33+,34-,35+,37-,38-,39-,40+/m0/s1 checkY
    Key: DANUORFCFTYTSZ-SJSJOXFOSA-N checkY
  • InChI=1/C40H68O11/c1-21-11-12-28(46-33(21)26(6)36(42)43)17-29-18-30(45-10)27(7)40(48-29)25(5)19-38(9,51-40)32-13-14-37(8,49-32)35-23(3)16-31(47-35)34-22(2)15-24(4)39(44,20-41)50-34/h21-35,41,44H,11-20H2,1-10H3,(H,42,43)/t21-,22-,23-,24+,25+,26+,27+,28+,29+,30+,31+,32+,33+,34-,35+,37-,38-,39-,40+/m0/s1
    Key: DANUORFCFTYTSZ-SJSJOXFOBS
  • OC(=O)[C@H](C)[C@@H]1O[C@H](CC[C@@H]1C)C[C@H]6O[C@]2(O[C@@](C)(C[C@H]2C)[C@H]3CC[C@](C)(O3)[C@@H]4O[C@H](C[C@@H]4C)[C@H]5O[C@@](O)(CO)[C@H](C)C[C@@H]5C)[C@H](C)[C@H](OC)C6
Properties
Chemical formula
C40H68O11
Molar mass 724.96132 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Chemical compound

Nigericin is an antibiotic derived from Streptomyces hygroscopicus. Its isolation from soil from Nigeria was described in the 1950s, by R.L Harned (et. al),[1][2] and in 1968 the structure could be elucidated by X-ray crystallography.[3] The structure and properties of nigericin are similar to the antibiotic monensin. Commercially it is obtained as a byproduct, or contaminant, at the fermentation of geldanamycin. It is also called polyetherin A, azalomycin M, helixin C, antibiotic K178, and antibiotic X-464.

Nigericin acts as an H+, K+, Pb2+ ionophore. Most commonly it is an antiporter of H+ and K+.

In the past nigericin was used as an antibiotic active against gram positive bacteria. It inhibits the Golgi functions in Eukaryotic cells. Its ability to induce K+ efflux also makes it a potent activator of the NLRP3 inflammasome[4][5]

References

  1. ^ Harned, R. L.; Hidy, P. H.; Corum, C. J.; Jones, K. L. (December 1951). "Nigericin a new crystalline antibiotic from an unidentified Streptomyces". Antibiotics & Chemotherapy (Northfield, Ill.). 1 (9): 594–596. ISSN 0570-3123. PMID 24541690.
  2. ^ Graven SN, Estrada-O S, Lardy HA (1966). "Alkali metal cation release and respiratory inhibition induced by nigericin in rat liver mitochondria". Proc. Natl. Acad. Sci. U.S.A. 56 (2): 654–8. Bibcode:1966PNAS...56..654G. doi:10.1073/pnas.56.2.654. PMC 224422. PMID 5229984.
  3. ^ Steinrauf LK, Pinkerton M, Chamberlin JW (1968). "The structure of nigericin". Biochem. Biophys. Res. Commun. 33 (1): 29–31. doi:10.1016/0006-291X(68)90249-0. PMID 5696503.
  4. ^ Mariathasan, S; Weiss, DS; Newton, K; McBride, J; O'Rourke, K; Roose-Girma, M; Lee, WP; Weinrauch, Y; Monack, DM; Dixit, VM (9 March 2006). "Cryopyrin activates the inflammasome in response to toxins and ATP". Nature. 440 (7081): 228–32. Bibcode:2006Natur.440..228M. doi:10.1038/nature04515. PMID 16407890.
  5. ^ Muñoz-Planillo, R; Kuffa, P; Martínez-Colón, G; Smith, BL; Rajendiran, TM; Núñez, G (27 June 2013). "K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter". Immunity. 38 (6): 1142–53. doi:10.1016/j.immuni.2013.05.016. PMC 3730833. PMID 23809161.

External links

  • Commercial supplier of nigericin, free acid or Sodium salt
  • v
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Nonribosomally synthesized porters (TC 2B)
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  • e
GABATooltip γ-Aminobutyric acid metabolism and transport modulators
Transporter
GATTooltip GABA transporter
VIAATTooltip Vesicular inhibitory amino acid transporter
Enzyme
GADTooltip Glutamate decarboxylase
GABA-TTooltip γ-Aminobutyrate aminotransferase
Other
Antivitamin B6
See also
Receptor/signaling modulators
GABA receptor modulators
GABAA receptor positive modulators
Glutamate metabolism/transport modulators
  • v
  • t
  • e
Transporter
EAATsTooltip Excitatory amino acid transporters
vGluTsTooltip Vesicular glutamate transporters
Enzyme
GAHTooltip Glutamine aminohydrolase (glutaminase)
  • BPTES
  • CB-839
  • DON
ASTTooltip Aspartate aminotransferase
  • 2-Amino-3-butenoic acid
  • AAOA
  • AMB
  • β-DL-Methylene-aspartate
  • Hydrazinosuccinate
ALTTooltip Alanine aminotransferase
  • β-Chloro-L-alanine
  • L-Cycloserine
  • Propargylglycine
GDHTooltip Glutamate dehydrogenase
GSTooltip Glutamine synthetase
GADTooltip Glutamate decarboxylase
See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators • GABA metabolism and transport modulators