Specific interaction of lipoate at the active site of rhodanese

Dihydrolipoate is an acceptor of the rhodanese-bound sulfane sulfur atom, a s shown by analysis of the elementary steps of the reaction catalyzed by rh odanese. The crystal structure of sulfur-substituted rhodanese complexed wi th the non-reactive oxidized form of lipoate has revealed that the compound is bound at the enzyme active site, with the dithiolane ring buried in the interior of the cavity and the carboxylic end pointing towards the solvent . One of the sulfur atoms of the ligand in the unproductive complex is rela tively close to the sulfane sulfur bound to Cys-247, the sulfur that is tra nsferred during the catalytic reaction. This mode of binding of lipoate is likely to mimic that of dihydrolipoate. The results presented here support the possible role of dihydrolipoate as sulfur-acceptor substrate of rhodane se in an enzymatic reaction that might serve to provide iron-sulfur protein s with inorganic sulfide. (C) 2000 Elsevier Science B.V. All rights reserve d.