Drug transporters

Transporters are molecules that transport small molecules (di- and tripeptides, saccharides and neurotransmitters) over membranes. The organism contains a large number of transporters, which have been shown to be important for the function of human cells. Transporters are considered very important drug targets for the future. The antidepressive drug citalopram is an inhibitor of the serotonin transporter, and antibacterial such as penicillins are actively transported across membranes by peptide transporters.

We are working on several transporters, applying both experimental and computational methods. Experimentally we have cloned, expressed and purified several bacterial amino acid and peptide transporters. The aim of this activity is to determine the 3D structure of membrane-bound bacterial transporters and use these as models for the corresponding eukaryote transporters. 3D models of several eukaryote peptide and neurotransmitter transporters have already been constructed by computational methods.

Based on these models we have been able to explain the structure-activity relationships for various types of ligands and predict mutations to gain further knowledge on the translocation mechanism.

Human serotonin transporter

3D model of the human serotonin transporter with the anti-depressive drug escitalopram in the proposed recognition site.