5ol4 | pdb_00005ol4

1.28 A resolution of Sporosarcina pasteurii urease inhibited in the presence of NBPT

spinqualitylabelsall models 5ol4, resolution 1.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ol4 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 1.28Å Ligands: 9XN, CXM, EDO, KCX, NI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function URE3_SPOPA Publication Abstract from PubMed The nickel-dependent enzyme urease is a virulence factor for a large number of pathogenic and antibiotic-resistant bacteria, as well as a negative factor for the efficiency of soil nitrogen fertilization for crop production. The use of urease inhibitors to offset these effects requires knowledge, at a molecular level, of their mode of action. The 1.28 A resolution structure of the enzyme-inhibitor complex obtained upon incubation of Sporosarcina pasteurii urease with N-(n-butyl)thiophosphoric triamide (NBPT), a molecule largely utilized in agriculture, reveals the presence of the monoamidothiophosphoric acid (MATP) moiety, obtained upon enzymatic hydrolysis of the diamide derivative of NBPT (NBPD) to yield n-butyl amine. MATP is bound to the two Ni(II) ions in the active site of urease using a mu2-bridging O atom and terminally bound O and NH2 groups, with the S atom of the thiophosphoric amide pointing away from the metal center. The mobile flap modulating the size of the active site cavity is found in the closed conformation. Docking calculations suggest that the interaction between urease in the open flap conformation and NBPD involves a role for the conserved alphaArg339 in capturing and orienting the inhibitor prior to flap closure. Calorimetric and spectrophotometric determinations of the kinetic parameters of this inhibition indicate the occurrence of a reversible slow inhibition mode of action, characterized, for both bacterial and plant ureases, by a very small value of the dissociation constant of the urease-MATP complex. No need to convert NBPT to its oxo derivative NBPTO, as previously proposed, is necessary for urease inhibition. Urease Inhibition in the Presence of N-(n-Butyl)thiophosphoric Triamide, a Suicide Substrate: Structure and Kinetics.,Mazzei L, Cianci M, Contaldo U, Musiani F, Ciurli S Biochemistry. 2017 Oct 10;56(40):5391-5404. doi: 10.1021/acs.biochem.7b00750., Epub 2017 Sep 15. PMID:28857549 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Urease 3D structures

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