Marianne von Glehn

Three-dimensional structure of oligomycin B

The antibiotic oligomycin has been demonstrated by Lardy et al. [ 1] .to act as a potent inhibitor of oxidative phosphorylation. As the first specific inhibitor acting at the site of coupling between respiration and phosphorylation, oligomycin has become a most valuable tool for investigating the mechanism of this process, and has as such been widely used over the past years in studies with mitochondria [2], submitochondrial particles [3] and purified enzymes [4] . Its precise mode of action, however, has not yet been understood, and progress to this end has been seriously limited by the lack of knowledge of the structure of oligomycin. Preparations of oligomycin contain 3 molecular species, denoted A, B and C, which all inhibit oxidative phosphorylation with equal efficiencies [5] . By chemical studies of degradation products of purified oligomycin B, parts of its structure have been determined by Prouty et al, [6]. These studies have indicated that the molecule, with an observed chemical composition C4sHn 01*, consists of a large, 25or 26-membered, heterocyclic ring containing 3 double-bonds. The ring also contains keto, hydroxy and methyl substituents, and is linked to 2 saturated, hetero-atomic, 6-membered rings. The present paper reports the three-dimensional structure of oligomycin B, as determined from singlecrystal X-ray diffraction data.