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Substrate recognition and translocation by polyspecific organic cation transporters
-
Hermann Koepsell
Published/Copyright:
June 18, 2011
Abstract
Organic cation transporters (OCTs) of the SLC22 family play a pivotal role in distribution and excretion of cationic drugs. They mediate electrogenic translocation of cations in both directions. OCTs are polyspecific transporters. During substrate translocation they perform a series of conformational changes involving an outward-facing conformation, an occluded state and an inward-facing conformation. Mutagenesis of OCT1 in combination with homology modeling showed that identical amino acids form the innermost parts of the outward-open and inward-open binding clefts. In addition to low affinity substrate binding sites, OCT1 contains high affinity substrate binding sites that can mediate inhibition via non-transported compounds.
Keywords: organic cation transporters; polyspecific transporters; substrate recognition; transport mechanism
Received: 2010-9-14
Accepted: 2010-10-11
Published Online: 2011-06-18
Published in Print: 2011-02-01
©2011 by Walter de Gruyter Berlin New York
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Keywords for this article
organic cation transporters;
polyspecific transporters;
substrate recognition;
transport mechanism
Articles in the same Issue
- Publisher’s Note
- Publisher’s Note
- Guest Editorial
- Highlight: Membrane transport in light of structure, function, and evolution
- HIGHLIGHT: MEMBRANE TRANSPORT IN LIGHT OF STRUCTURE, FUNCTION, AND EVOLUTION
- Pathways of transport protein evolution: recent advances
- Evolution of YidC/Oxa1/Alb3 insertases: three independent gene duplications followed by functional specialization in bacteria, mitochondria and chloroplasts
- Omp85 in eukaryotic systems: one protein family with distinct functions
- Evolution of ABC transporters by gene duplication and their role in human disease
- A structural and functional analysis of type III periplasmic and substrate binding proteins: their role in bacterial siderophore and heme transport
- The multidrug transporter Pdr5: a molecular diode?
- The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?
- Pumping lipids with P4-ATPases
- Transporters, Trojan horses and therapeutics: suitability of bile acid and peptide transporters for drug delivery
- Substrate recognition and translocation by polyspecific organic cation transporters
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine
- SLC22 transporter family proteins as targets for cytostatic uptake into tumor cells
- Role of the Ca2+-activated Cl- channels bestrophin and anoctamin in epithelial cells
- Single-molecule fluorescence resonance energy transfer techniques on rotary ATP synthases
- Structure determination of channel and transport proteins by high-resolution microscopy techniques
