Journal:JBSD:6

Evidence-based docking of the urease activation complex

Rodrigo Ligabue-Braun, Rafael Real-Guerra, Célia Regina Carlini, Hugo Verli^[1]

Molecular Tour
Ureases are enzymes that break down urea to carbon dioxide and ammonia, and they are one of the very few enzymes that have nickel in their active sites. Genetic and biochemical studies have shown that most of these enzymes require accessory proteins for the correct assembly of the nickel in their metallocenters. UreA (green), UreB (red), and UreC (darkmagenta) form the (UreABC)3 apoprotein. The trimeric representation considers UreABC as a functional unit. Studies of Klebsiella aerogenes urease activation pathway revealed that three accessory proteins – UreD (yellow), UreF (cyan), UreG (magenta) – are essential for the production of a functional urease. These proteins sequentially bind to form the (UreABC-UreD)3, (UreABC-UreDF)3, and (UreABC-UreDFG)3 activation complexes. Click here to see this structure is rotated by 90º. In this work we submitted structural models of such proteins to macromolecular docking calculations with K. aerogenes urease, which lead to a putative structure for the urease activation complex. The presented model for this complex is the first to include UreG and to use the current data on the activation pathway to guide the docking calculations. Despite the urease activation process being far more complex, our results are likely to expand the current knowledge on this essential step for proper ureolytic activity, aiding further high resolution studies of this macromolecular assembly by providing a 3D scaffold to work upon.