Molecular Dynamics Study ofHelicobacter pyloriUrease.
Helicobacter pylorihave 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 theH. pyloriurease 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 onKlebsiella aerogenes[Roberts et al.J. Am. Chem. Soc.2012,134, 9934] urease has been identified in theH. pylorienzyme 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.
Department of Chemistry, Quantum Theory Project, 2328 New Physics Building, University of Florida , Gainesville, Florida 32611-8435, United States.
Mona S
MS
Minkara
Department of Chemistry, Quantum Theory Project, 2328 New Physics Building, University of Florida , Gainesville, Florida 32611-8435, United States.
Melek N
MN
Ucisik
Department of Chemistry, Quantum Theory Project, 2328 New Physics Building, University of Florida , Gainesville, Florida 32611-8435, United States.
Michael N
MN
Weaver
Department of Chemistry, Department of Biochemistry and Molecular Biology, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824-1322, United States.
Kenneth M
KM
Merz