Comparative modeling of the human monoamine transporters: similarities in substrate binding.

ABSTRACT: The amino acid compositions of the substrate binding pockets of the three human monoamine transporters are compared as is the orientation of the endogenous substrates, serotonin, dopamine, and norepinephrine, bound in these. Through a combination of homology modeling, induced fit dockings, molecular dynamics simulations, and uptake experiments in mutant transporters, we propose a common binding mode for the three substrates. The longitudinal axis of the substrates is similarly oriented with these, forming an ionic interaction between the ammonium group and a highly conserved aspartate, Asp98 (serotonin transporter, hSERT), Asp79 (dopamine transporter, hDAT), and Asp75 (norepinephrine transporter, hNET). The 6-position of serotonin and the para-hydroxyl groups of dopamine and norepinephrine

SUBMITTER: Koldso H 

PROVIDER: S-EPMC3582297 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature