Journal:JBIC:20

<scene name='Journal:JBIC:20/Cv/3'>Urease</scene>, the enzyme that catalyses the hydrolysis of urea, is a virulence factor for a large number of ureolytic bacterial human pathogens. The increasing resistance of these pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilisation in agricultural applications, has stimulated the development of novel classes of molecules that target urease as enzyme inhibitors. We report on the crystal structure of a <scene name='Journal:JBIC:20/Cv/4'>complex formed between citrate and urease</scene> from ''Sporosarcina pasteurii'', a widespread and highly ureolytic soil bacterium, with 1.50 Å resolution. The fit of the ligand to the <scene name='Journal:JBIC:20/Cv/8'>active site</scene> involves stabilising interactions, such as a carboxylate group that binds the nickel ions at the active site and several hydrogen bonds with the surrounding residues. The <font color='blue'><b>nitrogen</b></font>, <font color='red'><b>oxygen</b></font> and <span style="color:green;background-color:black;font-weight:bold;">nickel</span> atoms are <font color='blue'><b>blue</b></font>, <font color='red'><b>red</b></font>, and <span style="color:green;background-color:black;font-weight:bold;">green</span>, respectively. <span style="color:yellow;background-color:black;font-weight:bold;">The carbon atoms of citrate are in yellow</span>. The <scene name='Journal:JBIC:20/Cv/9'>citrate ligand has a significantly extended structure</scene> compared with previously reported ligands co-crystallised with urease and thus represents a unique and promising scaffold for the design of new, highly active, stable, selective inhibitors. <font color='darkmagenta'><b>The residues which interact with Ni and OH are in darkmagenta, of note, His249, His139, and Kcx220<ref>Kcx - Lysine NZ-carboxylic acid</ref></b></font>, whereas <font color='magenta'><b>the residues which interact with citrate are in magenta</b></font>.

<scene name='Journal:JBIC:20/Cv/3'>Urease</scene>, the enzyme that catalyses the hydrolysis of urea, is a virulence factor for a large number of ureolytic bacterial human pathogens. The increasing resistance of these pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilisation in agricultural applications, has stimulated the development of novel classes of molecules that target urease as enzyme inhibitors. We report on the crystal structure of a <scene name='Journal:JBIC:20/Cv/4'>complex formed between citrate and urease</scene> from ''Sporosarcina pasteurii'', a widespread and highly ureolytic soil bacterium, with 1.50 Å resolution. The fit of the ligand to the <scene name='Journal:JBIC:20/Cv/8'>active site</scene> involves stabilising interactions, such as a carboxylate group that binds the nickel ions at the active site and several hydrogen bonds with the surrounding residues. The <font color='blue'><b>nitrogen</b></font>, <font color='red'><b>oxygen</b></font> and <span style="color:green;background-color:black;font-weight:bold;">nickel</span> atoms are <font color='blue'><b>blue</b></font>, <font color='red'><b>red</b></font>, and <span style="color:green;background-color:black;font-weight:bold;">green</span>, respectively. <span style="color:yellow;background-color:black;font-weight:bold;">The carbon atoms of citrate are in yellow</span>. The <scene name='Journal:JBIC:20/Cv/9'>citrate ligand has a significantly extended structure</scene> compared with previously reported ligands co-crystallised with urease and thus represents a unique and promising scaffold for the design of new, highly active, stable, selective inhibitors. <font color='darkmagenta'><b>The residues which interact with Ni and OH are in darkmagenta, of note, His249, His139, and Kcx220<ref>Kcx - Lysine NZ-carboxylic acid</ref></b></font>, whereas <font color='magenta'><b>the residues which interact with citrate are in magenta</b></font>.

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</StructureSection>

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