Stigmatellin is a potent

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of the quinol oxidation (Qo) site of the

cytochrome bc1 Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bi ...

complex in

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and the

cytochrome b6f The cytochrome ''b''6''f'' complex (plastoquinol—plastocyanin reductase; ) is an enzyme found in the thylakoid membrane in chloroplasts of plants, cyanobacteria, and green algae, that catalyzes the transfer of electrons from plastoquinol to ...

complex of thylakoid membranes. At higher concentrations, stigmatellin also inhibits Complex I, as a "Class B" inhibitor of that enzyme. 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 ''Paracoccus denitrificans'', is a coccoid bacterium known for its nitrate reducing properties, its ability to replicate under conditions of hypergravity and for being a relative of the eukaryotic mitochondrion (endosymbiotic theory). Descripti ...

'') 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 In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

to histidine residue 181 (His-181), a ligand to the Fe2Siron-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

Further reading