The crystal structure of Sporosarcina pasteurii urease in a complex with citrate provides new hints for inhibitor design
Stefano Benini, Paulina Kosikowska, Michele Cianci, Luca Mazzei, Antonio Gonzalez Vara,
Łukasz Berlicki, and Stefano Ciurli [1]
Molecular Tour
, the enzyme that catalyses the hydrolysis of urea, is a virulence factor for a large number of ureolytic bacterial human pathogens. The increasing resistance of these pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilisation in agricultural applications, has stimulated the development of novel classes of molecules that target urease as enzyme inhibitors. We report on the crystal structure of a from Sporosarcina pasteurii, a widespread and highly ureolytic soil bacterium, with 1.50 Å resolution. The fit of the ligand to the involves stabilising interactions, such as a carboxylate group that binds the nickel ions at the active site and several hydrogen bonds with the surrounding residues. The nitrogen, oxygen and nickel atoms are blue, red, and green, respectively. The carbon atoms of citrate are in yellow. The compared with previously reported ligands co-crystallised with urease and thus represents a unique and promising scaffold for the design of new, highly active, stable, selective inhibitors. The residues which interact with Ni and OH are in darkmagenta, of note, His249, His139, and Kcx220[2], whereas the residues which interact with citrate are in magenta.
PDB reference: The crystal structure of Sporosarcina pasteurii urease in complex with citrate, 4ac7
