Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

Determining the type of interaction between zebrafish Oct1 and endo- and xenobiotics (CROSBI ID 637211)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa

Mihaljević, Ivan ; Popović, Marta ; Žaja, Roko ; Maraković, Nikola ; Smital, Tvrtko Determining the type of interaction between zebrafish Oct1 and endo- and xenobiotics // Abstract Book - International FishMed Conference on Zebrafish Research / Bialek-Wyrzykowska, Urszula (ur.). Varšava: International Institute of Molecular and Cell Biology in Warsaw, 2016. str. 64-64

Podaci o odgovornosti

Mihaljević, Ivan ; Popović, Marta ; Žaja, Roko ; Maraković, Nikola ; Smital, Tvrtko

engleski

Determining the type of interaction between zebrafish Oct1 and endo- and xenobiotics

Organic cation transporters (OCT) are polyspecific membrane transporters from Solute Carrier superfamily (SLC), present in all vertebrates, where they play crucial role in homeostasis of organic cations, which encompass various endo- and xenobiotics. There are two Oct members in zebrafish, in respect to three members present from reptiles to human. Oct1 in zebrafish is dominantly expressed in kidney and liver, which indicates its potential compensatory role of human OCT1 and OCT2, which are dominantly expressed in liver and kidney, respectively. In our previous research we developed in vitro assay for functional characterization of Oct1, based on heterologous expression system in HEK293T cells. Using fluorescent substrates, we identified various interactors ranging from physiological compounds such as steroid hormones to the environmental contaminants such as organotin compounds and various pharmaceuticals. In present study, we tried to determine the type of interaction with previously identified interactors using classic Michaelis-Menten kinetics. However, results revealed mixed type of interaction with several compounds, pointing to more complex active region of Oct1. In order to characterize Oct1 active region in more detail, we performed homology modeling and molecular docking and identified potentially crucial amino acid residues. These amino acids are also conserved within active region of human OCT1 and 2, which further confirms their crucial role. We determined that Lys215, Trp218, Arg440 and Ser470 have important role as donors of hydrogen atom in H-bond, whereas Phe160, Ser163, Leu164, Thr443, Gln447 and Cys550 contribute to formation of H-bond as acceptors of hydrogen atom. Amino acid residues Phe160, Tyr170, Trp219, Trp355, Arg440, and Phe447 were shown to form aromatic bonds between Oct1 and tested compounds. Our further research will focus on determination of roles these amino acid residues play within active region using site-directed mutagenesis.

Slc22 ; Oct1 ; zebrafish ; functional characterization ; homology modeling

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

64-64.

2016.

objavljeno

Podaci o matičnoj publikaciji

Abstract Book - International FishMed Conference on Zebrafish Research

Bialek-Wyrzykowska, Urszula

Varšava: International Institute of Molecular and Cell Biology in Warsaw

Podaci o skupu

International FishMed Conference on Zebrafish Research

poster

18.03.2016-19.03.2016

Varšava, Poljska

Povezanost rada

Kemija, Biologija