title: Crystal structures of MdfA complexed with acetylcholine and inhibitor reserpine.
abstract: The DHA12 family of transporters contains a number of prokaryotic and eukaryote membrane proteins. Some of these proteins share conserved sites intrinsic to substrate recognition, structural stabilization and conformational changes. For this study, we chose the MdfA transporter as a model DHA12 protein to study some general characteristics of the vesicular neurotransmitter transporters (VNTs), which all belong to the DHA12 family. Two crystal structures were produced forE. coliMdfA, one in complex with acetylcholine and the other with potential reserpine, which are substrate and inhibitor of VNTs, respectively. These structures show that the binding sites of these two molecules are different. The Ach-binding MfdA is mainly dependent on D34, while reserpine-binding site is more hydrophobic. Based on sequence alignment and homology modelling, we were able to provide mechanistic insights into the association between the inhibition and the conformational changes of these transporters.
authors.affiliation: College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457 China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: National Laboratory of Macromolecules, National Center of Protein Science - Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Heng
authors.affiliation: National Laboratory of Macromolecules, National Center of Protein Science - Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: National Laboratory of Macromolecules, National Center of Protein Science - Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.
authors.forename: Xianping
authors.initials: X
authors.lastname: Wang
keywords: Acetylcholine; Antiporter; DHA12; MdfA; Reserpine