7P7N

X-RAY CRYSTAL STRUCTURE OF SPOROSARCINA PASTEURII UREASE INHIBITED BY THE GOLD(I)-PHOSPHINE COMPOUND Au(PEt3)I DETERMINED AT 1.80 ANGSTROMS

This is a non-PDB format compatible entry.

Summary for 7P7N

• Entry DOI: 10.2210/pdb7p7n/pdb
• Descriptor: Urease subunit gamma, Urease subunit beta, Urease subunit alpha, ... (10 entities in total)
• Functional Keywords: urease, nickel, gold, enzyme, urea, hydrolase
• Biological source: Sporosarcina pasteurii; More
• Total number of polymer chains: 3
• Total formula weight: 89920.78

Authors

Mazzei, L.,Ciurli, S. (deposition date: 2021-07-20, release date: 2022-06-01, Last modification date: 2024-01-31)

Primary citation

Mazzei, L.,Massai, L.,Cianci, M.,Messori, L.,Ciurli, S.
Medicinal Au(I) compounds targeting urease as prospective antimicrobial agents: unveiling the structural basis for enzyme inhibition.
Dalton Trans, 50:14444-14452, 2021

PubMed Abstract: A few gold compounds were recently found to show antimicrobial properties , holding great promise for the discovery of new drugs to overcome antibiotic resistance. Here, the inhibition of the bacterial virulence factor urease by four Au(I)-compounds, namely Au(PEt)Cl, Au(PEt)Br, Au(PEt)I and [Au(PEt)]Cl, obtained from the antiarthritic Au(I)-drug Auranofin and earlier reported to act as antimicrobials, is investigated. The three monophosphino Au(I) complexes showed IC values in the 30-100 nM range, while the diphosphino Au(I) complex, though being less active, still showed a IC value of 7 μM. The structural basis for this inhibition was provided by solving the crystal structures of urease co-crystallized with Au(PEt)I and [Au(PEt)]Cl: at least two Au(I) ions bind the enzyme in a flap domain involved in the catalysis, thus obliterating enzyme activity. Peculiar changes observed in the two structures reveal implications for the mechanism of soft metal binding and enzyme inactivation.

PubMed: 34585201
DOI: 10.1039/d1dt02488d

Experimental method

X-RAY DIFFRACTION (1.8 Å)