For organisms to be able to survive it is important that they can detect and respond to changes in the environment. Sensor proteins present inside cells can interact with external stimuli triggering structural changes that can then be transferred to downstream signaling proteins via protein-protein interactions. Our research interest is in the mechanism of bacterial response to oxidative and nitrosative stress through the superfamily of sensor histidine kinases (HnoK) proteins, which can interact with stimuli through their own sensor domain or through an independent nitric oxide-sensing protein. HnoKs are important proteins for the bacterial signaling, for they mediate physiological responses such as bacterial chemotaxis, quorum sensing and biofilm formation. This process often involves sensing of signal by the sensor domain or protein which can regulate phosphorylation of a conserved histidine residue and thereby regulate the bacterial pathogenicity and environmental persistence. One family of such sensor proteins is Heme Nitric Oxide/ Oxygen binding proteins (H-NOXs), which are responsive to binding of heme with nitric oxide (NO) or oxygen (O2). Interestingly, our recent experimental studies revealed that H-NOX of cholera-causing bacteria named Vibrio cholerae can also act as a redox sensor by utilizing a conserved zinc site via a ligand-switch mechanism. Using NVIDIA graphics processing unit (GPU)-accelerated molecular dynamics simulations, we aim to identify the molecular mechanism of such newly discovered redox control in Vibrio cholerae H-NOX. Accordingly, in the presented poster we will describe the results of our investigation of the structural and dynamical mechanistic details for the inhibiting activity of reduced and oxidized forms H-NOX, as well as outline a strategy of expanding this study to other pathogenic bacteria.

Molecular dynamics studies of Vibrio cholerae protein H-NOX

255th National Meeting (2018)

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