Mona Minkara - Molecular Dynamics Study of Helicobacter pylori Urease

Version 2

      Publication Details (including relevant citation   information):

      Minkara, M. S.; Ucisik, M. N.;   Weaver, M. N.; Merz, K. M. Jr. “Molecular Dynamics Study of   Helicobacter pylori Urease” J. Theory   Comput. 2014, 10,   1852-1862.

      Abstract:

        Helicobacter pylori have   been implicated in an array of gastrointestinal disorders   including, but not limited to, gastric and duodenal ulcers and   adenocarcinoma. This bacterium utilizes an enzyme, urease, to   produce copious amounts of ammonia through urea hydrolysis in   order to survive the harsh acidic conditions of the stomach.   Molecular dynamics (MD) studies on the H.   pylori urease   enzyme have been employed in order to study structural features   of this enzyme that may shed light on the hydrolysis mechanism. A   total of 400 ns of MD simulation time were collected and analyzed   in this study. A wide-open flap state previously observed in MD   simulations on Klebsiella   aerogenes [Roberts   et al. J.   Am. Chem. Soc. 2012134,   9934] urease has been identified in theH.   pylori enzyme   that has yet to be experimentally observed. Critical distances   between residues on the flap, contact points in the closed state,   and the separation between the active site Ni2+ ions   and the critical histidine α322 residue were used to characterize   flap motion. An additional flap in the active site was elaborated   upon that we postulate may serve as an exit conduit for   hydrolysis products. Finally we discuss the internal hollow   cavity and present analysis of the distribution of sodium ions   over the course of the simulation.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/ct5000023