CHEM-330: BiochemistryFinal TaskUrease InhibitionDr. Amjid IqbalAnthony Shoukat(13-01421)ContentIntroduction to urease……………………………………………………………………………3Structure of urease... .... .............................................. .................... .............................. ................................... ........…...3Inhibitors of urease …………………………………………………………………………........ .....4 Molecular pathology of asthma…………………………………………………………………..4 Hygiene hypothesis………………………………… ………… …………………………………….4Molecular mechanism of genes and inflammatory action of T helper cells in asthma…………..4Genes are involved in inflammatory action and remodeling of pathways respiratory………… ………..…………..7References………………………………………………………………………………………… …8Introduction to the enzyme urease:Urease is an enzyme that catalyzes the hydrolysis of urea to ammonia and carbamate; at a later stage, the carbamate spontaneously produces carbonic acid and an additional molecule of ammonia. Urease enzymes are part of the amidohydrolase and phosphotriestrease superfamily. It required the bonding of two nickel ions for its own activity, hence known as a nickel-dependent metalloenzyme. (NH2)2CO +H2O → NH3 + NH2COOHNH2COOH +H2O → H2CO3 + NH3Figure 1: Hydrolysis of urea to carbonic acid and ammonia by ureaseIn 1926, James Summer proposed that urease is a globulin-like protein and that this was the first time an enzyme had been crystallized from Canavalia ensiformis (jack bean). Urease is present in different organisms, including plants, certain bacteria, invertebrates and fungi. Bacterial source of urease enzyme: Lactobacillus ruminis, Lactobacillus fermentum, Lactobacillus reuri and Klebsiella aerogenes. The final source of urease is Rhizopus oryzae. There is 40% urease extracted from filamentous mushrooms. It can...... middle of paper ....... It leaves the bridging hydroxide. A nickel ion binds to two inhibitory oxygen atoms while the third oxygen points toward the cavity, away from the nickel ion. The binding of boric acid has no significant effect on the geometry and coordination of the Ni ion. Figure 5: BPU active site inhibited by boric acid. The oxygen atom of the Ni-bound inhibitor (1) receives an H-bond from Hisα222 (at 2.6 Å), the latter being protonated due to the interaction of Hisα222 with the NH peptide group of Aspα224 . The oxygen atom of the inhibitor bound to Ni(2) forms an H-bond with Alaα170 O (at 2.8 Å), while the distal OH group of the inhibitor is H-bonded to a molecule of water involved in an H-bond network with an additional solvent molecule and Alaα366 O. This molecular model presents how the active site of PBU is inhibited by boric acid. Dosage of this particular enzyme: Applications in various fields: