6i9y

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

spinqualitylabelsall models 6i9y, resolution 2.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6i9y is a 3 chain structure with sequence from Sporosarcina pasteurii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.14Å Ligands: AU, CXM, EDO, KCX, NI, OH, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function URE1_SPOPA Publication Abstract from PubMed 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 N(wedge)N or C(wedge)N and C(wedge)N(wedge)N ligands were tested for their inhibitory effects against Canavalia ensiformis (jack bean) urease. The results showed potent inhibition effects with IC50 values in the nanomolar range. The 2.14 A resolution crystal structure of Sporosarcina pasteurii urease inhibited by the most effective Au(III) compound [Au(PbImMe)Cl2]PF6 (PbImMe = 1-methyl-2-(pyridin-2-yl)-benzimidazole) reveals the presence of two Au ions bound to the conserved triad alphaCys322/alphaHis323/alphaMet367. 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. Inhibition Mechanism of Urease by Au(III) Compounds Unveiled by X-ray Diffraction Analysis.,Mazzei L, Wenzel MN, Cianci M, Palombo M, Casini A, Ciurli S ACS Med Chem Lett. 2019 Jan 4;10(4):564-570. doi: 10.1021/acsmedchemlett.8b00585., eCollection 2019 Apr 11. PMID:30996797 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Urease 3D structures

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