These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Kinetic and structural analysis of the inactivation of urease by mixed-ligand phosphine halide Ag(I) complexes.
    Author: Mazzei L, Cirri D, Cianci M, Messori L, Ciurli S.
    Journal: J Inorg Biochem; 2021 May; 218():111375. PubMed ID: 33711632.
    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(PEt3)X]4 (X = Cl, Br, I), and with the ionic species [Ag(PEt3)2]NO3, 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(PEt3)X]4 complexes, with IC50 values in the nanomolar range; the efficiency of the inhibition increases in the Cl- < Br- < I- order. The activity of JBU upon [Ag(PEt3)2]NO3 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 Ag…Ag 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.
    [Abstract] [Full Text] [Related] [New Search]