Editing Vesicular monoamine transporter (section)

====RES binding site====
Consistent with catecholamine-binding affinity, RES has a threefold higher affinity for VMAT2 than for VMAT1.<ref name="Chaudhry FA 2007"/><ref name="Erickson JD 1996"/> The RES binding site is known to be [[hydrophobic]], which is thought to contribute to ligand binding affinity.<ref name="Wimalasena, K. 2011"/> Methamphetamine binds to the RES site on VMATs.<ref name="VMAT2 amph vs meth" />

The current working model proposes that RES and the substrate bind to a single site in a pH-gradient modulated [[Conformation activity relationship|conformational]] structure of the transporter. The conformation occurs after the transport of one H<sup>+</sup> across the membrane and into the vesicle; proton transport drives the substrate recognition site from the lumen to the cytoplasmic surface of the vesicle for RES and substrate binding.<ref name="Wimalasena, K. 2011"/><ref name="Chaudhry FA 2007"/><ref name = "Darchen">{{cite journal |vauthors=Darchen F, Scherman D, Henry JP | year = 1989 | title = Reserpine binding to chromaffin granules suggests the existence of two conformations of the monoamine transporter | journal = Biochemistry | volume = 28 | issue = 4| pages = 1692–1697 | doi=10.1021/bi00430a040| pmid = 2719928 }}</ref> Methoxytetrabenazine (MTBZ) may bind to the RES binding site, based on studies indicating that RES significantly inhibited MTBZ-binding.<ref name="Wimalasena, K. 2011"/> Amiodarone is also believed to inhibit monoamine vesicular uptake by binding to the RES binding site.<ref name="Wimalasena, K. 2011"/>