6I9Y

The 2.14 A X-ray crystal structure of Sporosarcina pasteurii urease in complex with Au(I) ions

Summary for 6I9Y

• Entry DOI: 10.2210/pdb6i9y/pdb
• Descriptor: Urease subunit gamma, Urease subunit beta, Urease subunit alpha, ... (9 entities in total)
• Functional Keywords: urease, nickel, gold compounds, metal-based ndrugs, hydrolase
• Biological source: Sporosarcina pasteurii (Bacillus pasteurii); More
• Total number of polymer chains: 3
• Total formula weight: 88320.09

Authors

Mazzei, L.,Cianci, M.,Ciurli, S. (deposition date: 2018-11-26, release date: 2019-05-01, Last modification date: 2024-01-24)

Primary citation

Mazzei, L.,Wenzel, M.N.,Cianci, M.,Palombo, M.,Casini, A.,Ciurli, S.
Inhibition Mechanism of Urease by Au(III) Compounds Unveiled by X-ray Diffraction Analysis.
Acs Med.Chem.Lett., 10:564-570, 2019

PubMed Abstract: The nickel-dependent enzyme urease is a virulence factor for a large number of critical human pathogens, making this enzyme a potential target of therapeutics for the treatment of resistant bacterial infections. In the search for novel urease inhibitors, five selected coordination and organometallic Au(III) compounds containing NN or CN and CNN ligands were tested for their inhibitory effects against (jack bean) urease. The results showed potent inhibition effects with IC values in the nanomolar range. The 2.14 Å resolution crystal structure of urease inhibited by the most effective Au(III) compound [Au(PbImMe)Cl]PF (PbImMe = 1-methyl-2-(pyridin-2-yl)-benzimidazole) reveals the presence of two Au ions bound to the conserved triad αCys322/αHis323/αMet367. The binding of the Au ions to these residues blocks the movement of a flap, located at the edge of the active site channel and essential for enzyme catalysis, completely obliterating the catalytic activity of urease. Overall, the obtained results constitute the basis for the design of new gold complexes as selective urease inhibitors with future antibacterial applications.

PubMed: 30996797
DOI: 10.1021/acsmedchemlett.8b00585

Experimental method

X-RAY DIFFRACTION (2.14 Å)