Resistance to several toxic anions in Escherichia coli is conferred by the ars operon carried on plasmid R773. The gene products of this operon catalyze extrusion of antimonials and arsenicals from cells. In this paper, we report the determination of the overall fold for ArsC, a 16 kDa protein of the ars operon involved in the reduction of arsenate to arsenite, using multidimensional, multinuclear NMR. The protein is found to contain large regions of extensive mobility, particularly in the active site. A model fold, computed on the basis of a preliminary set of NOEs, was found to be structurally homologous to E. coli glutaredoxin, thiol transferases, and glutathione S-transferase. Some kinship to the structure of low molecular weight tyrosine phosphatases, based on rough topological similarity but more so on the basis of a common anion-binding-loop motif H-CX(n)R, was also detected. Although functional, secondary, and tertiary structural homology is observed with these molecules, no significant homology in primary structure was detected. The mobilities of the active site of ArsC and of other enzymes are discussed.