By a News Reporter-Staff News Editor at Life Science Weekly -- Research findings on Catecholamines are discussed in a new report. According to news reporting from Aarhus, Denmark, by NewsRx journalists, research stated, "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 news correspondents obtained a quote from the research from Aarhus University, "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 were found to face Ala173 in hSERT, Gly153 in hDAT, and Gly149 in hNET. Three rotations of the substrates around the longitudinal axis were identified. In each mode, an aromatic hydroxyl group of the substrates occupied equivalent volumes of the three binding pockets, where small changes in amino acid composition explains the differences in selectivity. Uptake experiments support that the 5-hydroxyl group of serotonin and the meta-hydroxyl group norepinephrine and dopamine are placed in the hydrophilic pocket around Ala173, Ser438, and Thr439 in hSERT corresponding to Gly149, Ser419, Ser420 in hNET and Gly153 Ser422 and Ala423 in hDAT. Furthermore, hDAT was found to possess an additional hydrophilic pocket around Ser149 to accommodate the para-hydroxyl group."
According to the news reporters, the research concluded: "Understanding these subtle differences between the binding site compositions of the three transporters is imperative for understanding the substrate selectivity, which could eventually aid in developing future selective medicines."
For more information on this research see: Comparative modeling of the human monoamine transporters: similarities in substrate binding. Acs Chemical Neuroscience, 2013;4(2):295-309. (American Chemical Society - www.acs.org; Acs Chemical Neuroscience - www.pubs.acs.org/journal/acncdm)
Our news journalists report that additional information may be obtained by contacting H. Koldso, Center for Insoluble Protein Structures (inSPIN) and Interdisciplinary Nanoscience Center (iNANO), Dept. of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark. Additional authors for this research include A.B. Christiansen, S. Sinning and B. Schiott (see also Catecholamines).
Keywords for this news article include: Aarhus, Europe, Denmark, Dopamine, Ethanolamines, Amino Alcohols, Catecholamines, Norepinephrine, Biogenic Amines, Organic Chemicals.
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