Katharina Jahnke
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Charge transport through membrane proteins
Principal investigator: Prof. Dr. Thorsten Koslowski Institute for Physical Chemistry, R 3020 Phone: +49 (0) 761 203 6228 |
Abstract
I research the urea transporting protein channel of Helicobacter pylori (H. pylori). H. pylori is a gram-negative spiral bacteria which causes gastric symptoms. It is moving to the gastric epithelial cells. The specific interaction between the bacterial adhesins and the cell receptors leads to a succesfull colonization. H. pyolori leaves cytotoxines which causes an enourmes tissue damage. As H. pylori is antibiotic resistant it is very difficult to treat. Unfortunately roughly half of the world population is infected with H. Pylori. 1,2
Although a pH-value less then 7.0 is deadly for the bacteria it survives in the stomach due to an inner-bacterial urease activity. This activity is controlled by HpUreI which is a pH-sensitve, innermembrane urea-channel. At a pH-value of 7.0 the protein channel is closed. The four histidines near the entrance of the protein channel are deprotonated at this pH-value. Urea cannot get into the channel. At a pH-value of 5.0 the before mentioned histidines are protonated. As a result the protein channel opens and the urea can get into the channel and go to the cytoplasmic urease. Due to hydrolysis, urea will be split into ammonia and carbon dioxide. The ammonia is neutralizing the protons which entered into the protein channel. I am MD-simulating this mechanism to find out how it works in detail. 1,3,4
References
[1] Cheng-Yen Kao, Bor-Shyang Sheu, and Jiunn-Jong Wu. Helicobacter pylori infection:An overview of bacterial virulence factors and pathogenesis.Biomedical Journal,39(1):14 – 23, 2016.
[2] Mona S. Minkara, Melek N. Ucisik, Michael N. Weaver, and Kenneth M. Merz.Molecular dynamics study of helicobacter pylori urease.Journal of Chemical Theoryand Computation, 10(5):1852–1862, 2014. PMID: 24839409.
[3] McNulty R. Munson K. Chen C.-K. Soltis S. M. Sachs G. Luecke H. Strugatsky, D.Structure of the proton-gated urea channel from the gastric pathogen helicobacterpylori.Nature, 493:255–258, 2013.
[4] Ulmschneider J. Luecke H. Ulmschneider M. B. McNulty, R. Mechanisms of moleculartransport through the urea channel of helicobacter pylori.Nat Commun., 4:2900,2013.
