The complex of Bacillus pasteurii urease with β-mercaptoethanol from X-ray data at 1.65-Å resolution

The structure of beta-mercaptoethanol-inhibited urease from Bacillus pasteurii, a highly ureolytic soil micro-organism, was solved at 1.65 Angstrom using synchrotron X-ray cryogenic diffraction data. The structure clearly shows the unexpected binding mode of beta-mercaptoethanol. which bridges the two nickel ions in the active site through the sulfur atom and chelates one Ni through the OH functionality. Another molecule of inhibitor forms a mixed disulfide with a Cys residue, thus sealing the entrance to the active site cavity by steric hindrance. The possible implications of the results on structure-based molecular design of new urease inhibitors are discussed.