The Absolute Configuration of Rhizopodin and Its Inhibition of Actin Polymerization by Dimerization

Abstract

Three's company: Rhizopodin is a cytostatic macrolide and a potent actin depolymerizer produced by the myxobacterium Myxococcus stipitatus. A crystal structure analysis of the rhizopodin/actin complex reveals that rhizopodin is a C2-symmetric bislactone (see formula). The ternary complex supports the mode of rhizopodin-induced actin dimerization and reveals the absolute configuration and biologically active conformation of this macrolide.