Stigmatellin

Stigmatellin
Names
Preferred IUPAC name
2-[(3S,4S,5S,6S,7E,9E,11E)-4,6-Dimethoxy-3,5,11-trimethyltrideca-7,9,11-trien-1-yl]-8-hydroxy-5,7-dimethoxy-3-methyl-4H-1-benzopyran-4-one
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.149.842 Edit this at Wikidata
MeSH Stigmatellin
  • InChI=1S/C30H42O7/c1-10-18(2)13-11-12-14-22(33-6)21(5)29(36-9)19(3)15-16-23-20(4)27(31)26-24(34-7)17-25(35-8)28(32)30(26)37-23/h10-14,17,19,21-22,29,32H,15-16H2,1-9H3/b13-11+,14-12+,18-10+/t19-,21+,22-,29-/m0/s1 checkY
    Key: UZHDGDDPOPDJGM-CVOZLMQJSA-N checkY
  • InChI=1/C30H42O7/c1-10-18(2)13-11-12-14-22(33-6)21(5)29(36-9)19(3)15-16-23-20(4)27(31)26-24(34-7)17-25(35-8)28(32)30(26)37-23/h10-14,17,19,21-22,29,32H,15-16H2,1-9H3/b13-11+,14-12+,18-10+/t19-,21+,22-,29-/m0/s1
    Key: UZHDGDDPOPDJGM-CVOZLMQJBZ
  • O=C\1c2c(O/C(=C/1C)CC[C@H](C)[C@H](OC)[C@H](C)[C@@H](OC)\C=C\C=C\C(=C\C)C)c(O)c(OC)cc2OC
Properties
C30H42O7
Molar mass 514.65 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Stigmatellin is a potent inhibitor of the quinol oxidation (Qo) site of the cytochrome bc1 complex in mitochondria[1] and the cytochrome b6f complex of thylakoid membranes. At higher concentrations, stigmatellin also inhibits Complex I, as a "Class B" inhibitor of that enzyme.[2]

Stigmatellin is isolated from the myxobacterium Stigmatella aurantica, and contains a 5,7-dimethoxy-8-hydroxychromone aromatic headgroup with a hydrophobic alkenyl chain in position 2. Crystal structures for stigmatellin-inhibited bc1 complex from bovine, avian, yeast (Saccharomyces cerevisiae) and bacterial (Rhodobacter capsulatus, Cereibacter sphaeroides, and Paracoccus denitrificans) sources are available. Stigmatellin binds at the cytochrome b Qo site in the '(heme) bl distal' position, and associates with the Rieske iron-sulfur protein via a hydrogen bond to histidine residue 181 (His-181), a ligand to the [2Fe2S] iron-sulfur cluster of this subunit. This association raises the midpoint potential of the iron-sulfur cluster from 290 to 540 mV and restricts movement of the cytoplasmic domain of the Rieske protein.

References

  1. ^ von Jagow G, Ohnishi T (June 1985). "The chromone inhibitor stigmatellin--binding to the ubiquinol oxidation center at the C-side of the mitochondrial membrane". FEBS Letters. 185 (2): 311–5. Bibcode:1985FEBSL.185..311V. doi:10.1016/0014-5793(85)80929-7. PMID 2987042. S2CID 37956153.
  2. ^ Fato R, Bergamini C, Bortolus M, Maniero AL, Leoni S, Ohnishi T, Lenaz G (May 2009). "Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1787 (5): 384–92. doi:10.1016/j.bbabio.2008.11.003. PMC 2724837. PMID 19059197.

Further reading