Prof. Mladen TZVETKOV
Universität Greifswald
Institut für Pharmakologie
Kontakt
Program
"Organic cation transporters at the end of the beginning"
The Solute Carrier Family 22 (SLC22) ranks among the largest families of membrane transporters. Members such as URAT1 and OCTN2 exhibit high substrate specificity. However, most SLC22 transporters are polyspecific, transporting substrates with highly variable chemical. The polyspecific SLC22 transporters include organic cation transporters (OCTs) and organic anion transporters (OATs), which potentially play a pivotal role in the hepatic and renal elimination of drugs. While the pharmacological roles of this polyspecific SLC22 transporters are extensive studied, their physiological functions and structural bases of their polyspecificity are not fully understood. Recently, there has been a rapid accumulation of cryo-EM data on polyspecific SLC22 transporters, including significant contributions from Vienna's Institute of Pharmacology.
Our group focuses on the pharmacogenetics of drug transporters, particularly OCT1 (SLC22A1). Common polymorphisms result in reduced OCT1 activity in approximately 9% of Europeans. We aim to understand how this genetically determined reduction in OCT1 activity affects drug therapy. We also use this naturally occurring deficiency to study OCT1's physiological roles directly in humans.
The first part of my talk will cover OCT1's pharmacological role, the impact of its deficiency, and its potential physiological functions. The second part will present our pre-cryo-EM research on OCT1's structure-function relationship. Finally, I plan to discuss how recent cryo-EM data enhance our understanding of OCT1's polyspecificity and the effects of common polymorphisms on its activity.
Host: Harald SITTE
Contact for questions: Helmut KUBISTA