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
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
100.212.814
UNII
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
Y Key: DANUORFCFTYTSZ-SJSJOXFOSA-N
Y 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
C 40 H 68 O 11
Molar mass
724.973 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
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
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
Nonribosomally synthesized porters (
TC 2B )
Transporter
GAT Tooltip GABA transporter VIAAT Tooltip Vesicular inhibitory amino acid transporter
Enzyme
GAD Tooltip Glutamate decarboxylase GABA-T Tooltip γ-Aminobutyrate aminotransferase
Other
Transporter
EAATs Tooltip Excitatory amino acid transporters vGluTs Tooltip Vesicular glutamate transporters
Enzyme
GAH Tooltip Glutamine aminohydrolase (glutaminase) AST Tooltip Aspartate aminotransferase ALT Tooltip Alanine aminotransferase GDH Tooltip Glutamate dehydrogenase GS Tooltip Glutamine synthetase GAD Tooltip Glutamate decarboxylase