Minkara Mona S, Ucisik Melek N, Weaver Michael N, Merz Kenneth M
Department of Chemistry, Quantum Theory Project, 2328 New Physics Building, University of Florida , Gainesville, Florida 32611-8435, United States.
Department of Chemistry, Department of Biochemistry and Molecular Biology, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824-1322, United States.
J Chem Theory Comput. 2014 May 13;10(5):1852-1862. doi: 10.1021/ct5000023. Epub 2014 Mar 25.
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 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 [Roberts et al. , , 9934] urease has been identified in the 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 Ni 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.
已发现其与一系列胃肠道疾病有关，包括但不限于胃溃疡、十二指肠溃疡和腺癌。这种细菌利用一种脲酶，通过尿素水解产生大量氨，以便在胃部恶劣的酸性环境中存活。已采用对脲酶的分子动力学（MD）研究来探究该酶的结构特征，这些特征可能有助于揭示水解机制。本研究共收集并分析了400纳秒的MD模拟时间。在尚未经实验观察到的该酶中，已识别出先前在[罗伯茨等人，，9934]脲酶的MD模拟中观察到的大开瓣状态。瓣上残基之间的关键距离、闭合状态下的接触点以及活性位点镍离子与关键组氨酸α322残基之间的间距用于表征瓣的运动。详细阐述了活性位点中的另一个瓣，我们推测它可能作为水解产物的出口通道。最后，我们讨论内部中空腔，并给出模拟过程中钠离子分布的分析。
