7B58

X-ray crystal structure of Sporosarcina pasteurii urease inhibited by Ag(PEt3)Cl determined at 1.72 Angstroms

This is a non-PDB format compatible entry.

Summary for 7B58

• Entry DOI: 10.2210/pdb7b58/pdb
• Descriptor: Urease subunit gamma, Urease subunit beta, Urease subunit alpha, ... (9 entities in total)
• Functional Keywords: urease, enzyme, nickel, silver, hydrolase
• Biological source: Sporosarcina pasteurii; More
• Total number of polymer chains: 3
• Total formula weight: 89152.82

Authors

Mazzei, L.,Cianci, M.,Ciurli, S. (deposition date: 2020-12-03, release date: 2021-10-13, Last modification date: 2024-01-31)

Primary citation

Mazzei, L.,Cirri, D.,Cianci, M.,Messori, L.,Ciurli, S.
Kinetic and structural analysis of the inactivation of urease by mixed-ligand phosphine halide Ag(I) complexes.
J.Inorg.Biochem., 218:111375-111375, 2021

PubMed Abstract: Soft metal ions can inactivate urease, a Ni(II)-dependent enzyme whose hydrolytic activity has significant implications in agro-environmental science and human health. Kinetic and structural studies of the reaction of Canavalia ensiformis urease (JBU) and Sporosarcina pasteurii urease (SPU) with Ag(I) compounds of general formula [Ag(PEt)X] (X = Cl, Br, I), and with the ionic species [Ag(PEt)]NO, revealed the role of the Ag(I) ion and its ligands in modulating the metal-enzyme interaction. The activity of JBU is obliterated by the [Ag(PEt)X] complexes, with IC values in the nanomolar range; the efficiency of the inhibition increases in the Cl < Br < I order. The activity of JBU upon [Ag(PEt)]NO addition decreases to a plateau corresponding to ca. 60% of the original activity and decreases with time at a reduced rate. Synchrotron X-ray crystallography on single crystals obtained after the incubation of SPU with the Ag(I) complexes yielded high-resolution (1.63-1.97 Å) structures. The metal-protein adducts entail a dinuclear Ag(I) cluster bound to the conserved residues αCys322, αHis323, and αMet367, with a bridging cysteine thiolate atom, a weak AgAg bond, and a quasi-linear Ag(I) coordination geometry. These observations suggest a mechanism that involves the initial substitution of the phosphine ligand, followed by a structural rearrangement to yield the dinuclear Ag(I) cluster. These findings indicate that urease, in addition to the active site dinuclear Ni(II) cluster, possesses a secondary metal binding site, located on the mobile flap domain, capable of recognizing pairs of soft metal ions and controlling catalysis.

PubMed: 33711632
DOI: 10.1016/j.jinorgbio.2021.111375

Experimental method

X-RAY DIFFRACTION (1.72 Å)