PMSA;phomopsin;PHOMOPSIN A;phomopsin a from phomopsis leptostromiformis;Phomopsin A, 98%, from Phomopsis leptostromiformis;Aspartic acid, (βS)-3-chloro-β,5-dihydroxy-N-methyl-L-tyrosyl-3,4-didehydro-L-valyl-3-hydroxy-L-isoleucyl-3,4-didehydro-L-prolyl-(2E)-2,3-didehydroisoleucyl-2,3-didehydro-, cyclic (15→3)-ether, (2E)-
Phomopsin A is a an acidic 13-membered cyclic hexapeptide-like metabolite with three unusual amino acids linked in an ‘ansa’ macrocycle with a tripeptide tail, terminating in a dicarboxylic acid. Phomopsin A is a potent mycotoxin produced by the fungus, Phomopsis leptostromiformis, and causes lupinosis in livestock fed infected lupins. Phomopsin A is an important bioprobe for understanding cellular structural proteins. It binds selectively to dimeric tubulin at a site overlapping that of vinblastine and maytansine, inhibiting the formation of the microtubule spindle to block cell division. Uniquely, phomopsin A protects tubulin from decay.
효소 저해제
This mycotoxin and antibiotic (FW = 789.24 g/mol; CAS 64925-80-0) is obtained from Diaporthe toxica (formerly Phomopsis leptostromiformis), a fungus that grows mainly within lupin stems, the consumption of which leads to lupinosis in sheep grazing on lupin stubble. Intoxication results in liver damage, disorientation, blindness, lethargy and death in severe cases. Phomopsin A is a 13-membered ether oxygen-containing macrolide that blocks tubulin polymerization (Ki <1 μM). It also inhibits vinblastine binding to tubulin and, in common with vinblastine and maytansine, enhances colchicine binding. Phomopsin A and the depsipeptide, Dolastatin 10, bind to a site adjacent to the vinca alkaloid and nucleotide sites. This mycotoxin induces tubulin oligomerization into ring structures that cannot form microtubules. Scatchard analysis suggests two classes of binding sites: a high-affinity site (K1 = 1 x 10–8 M) and a low-affinity site (K2 = 3 x 10–7 M). Phomopsin A also inhibits rhizoxin binding, with a Ki of 0.8 x 10–8 M, suggesting that the high-affinity site of phomopsin A is identical to the rhizoxin binding site. The development and validation of an LC-MS/MS method for detecting Phomopsin A in lupin and lupincontaining retail food has been reported.
