Ion Modulation in Secondary Transporters
atmire.migration.oldid | 4149 | |
dc.contributor.advisor | Noskov, Sergei | |
dc.contributor.author | Zdravkovic, Igor | |
dc.contributor.committeemember | Edwards, Robert Allan | |
dc.contributor.committeemember | Tieleman, Peter | |
dc.contributor.committeemember | Turner, Raymond J. | |
dc.contributor.committeemember | MacCallum, Justin Laine | |
dc.contributor.committeemember | Casey, Joseph Roman | |
dc.date.accessioned | 2016-02-02T19:40:49Z | |
dc.date.available | 2016-02-02T19:40:49Z | |
dc.date.issued | 2016-02-02 | |
dc.date.submitted | 2016 | en |
dc.description.abstract | Molecular transport across the cell membrane is an important and highly regulated process. Secondary transporters are a large family of integral membrane proteins responsible for mediating molecular exchange. Pre-existing ion gradients are utilized to drive secondary transport. Our focus was on the solute carrier (SLC) family of secondary transporters, specifically those that utilize Na+ to drive transport. The SLC family can be further classified as a sodium substrate symporter (SSS). Specifically, we focused on the human serotonin and dopamine transporters (SLC6) and iodide symporters (SLC5). The sodium electrochemical potential is coupled to the energetically unfavourable transport of the substrate. This yields a net favourable translocation of the substrate and co-transported ions. Little structural information is available on the SSS family transporters and even less when only the human variants are considered. This prompted an attempt to predict human protein structures using the available data from bacterial homologues to fill the knowledge gap. The methodology was based on the X-ray structures of the leucine transporter (LeuT) and sodium galactose transporter (vSGLT). Through our structural alignments we were able to identify the ion binding sites. With the help of Glide docking software, we successfully identified substrate and inhibitors binding sites. Molecular dynamics were used to simulate biologically relevant systems and find the forces driving substrate and ion binding. Our computational biochemistry approach has proven to be a reliable method to study the transport and substrate interactions. In addition, our collaborative efforts successfully merged theoretical and experimental science. | en_US |
dc.identifier.citation | Zdravkovic, I. (2016). Ion Modulation in Secondary Transporters (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26671 | en_US |
dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/26671 | |
dc.identifier.uri | http://hdl.handle.net/11023/2808 | |
dc.language.iso | eng | |
dc.publisher.faculty | Graduate Studies | |
dc.publisher.institution | University of Calgary | en |
dc.publisher.place | Calgary | en |
dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
dc.subject | Biology | |
dc.subject | Bioinformatics | |
dc.subject | Microbiology | |
dc.subject | Neuroscience | |
dc.subject | Biophysics | |
dc.subject | Biophysics--Medical | |
dc.subject | Mental Health | |
dc.subject | Pharmacology | |
dc.subject | Chemistry--Pharmaceutical | |
dc.subject.classification | Computational Biochemistry | en_US |
dc.title | Ion Modulation in Secondary Transporters | |
dc.type | doctoral thesis | |
thesis.degree.discipline | Biological Sciences | |
thesis.degree.grantor | University of Calgary | |
thesis.degree.name | Doctor of Philosophy (PhD) | |
ucalgary.item.requestcopy | true |