<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Papageorgiou, Ioannis</style></author><author><style face="normal" font="default" size="100%">Gournas, Christos</style></author><author><style face="normal" font="default" size="100%">Vlanti, Anna</style></author><author><style face="normal" font="default" size="100%">Amillis, Sotiris</style></author><author><style face="normal" font="default" size="100%">Pantazopoulou, Areti</style></author><author><style face="normal" font="default" size="100%">Diallinas, George</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Specific interdomain synergy in the UapA transporter determines its unique specificity for uric acid among NAT carriers.</style></title><secondary-title><style face="normal" font="default" size="100%">J Mol Biol</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Aspergillus nidulans</style></keyword><keyword><style  face="normal" font="default" size="100%">Binding Sites</style></keyword><keyword><style  face="normal" font="default" size="100%">Fungal</style></keyword><keyword><style  face="normal" font="default" size="100%">Fungal Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes</style></keyword><keyword><style  face="normal" font="default" size="100%">Kinetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Membrane Transport Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Models</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutagenesis</style></keyword><keyword><style  face="normal" font="default" size="100%">Nucleobase Transport Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Structure</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Homology</style></keyword><keyword><style  face="normal" font="default" size="100%">Site-Directed</style></keyword><keyword><style  face="normal" font="default" size="100%">Tertiary</style></keyword><keyword><style  face="normal" font="default" size="100%">Uric Acid</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2008</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2008 Oct 24</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">382</style></volume><pages><style face="normal" font="default" size="100%">1121-35</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">UapA, a uric acid-xanthine permease of Aspergillus nidulans, has been used as a prototype to study structure-function relationships in the ubiquitous nucleobase-ascorbate transporter (NAT) family. Using novel genetic screens, rational mutational design, chimeric NAT molecules, and extensive transport kinetic analyses, we show that dynamic synergy between three distinct domains, transmembrane segment (TMS)1, the TMS8-9 loop, and TMS12, defines the function and specificity of UapA. The TMS8-9 loop includes four residues absolutely essential for substrate binding and transport (Glu356, Asp388, Gln408, and Asn409), whereas TMS1 and TMS12 seem to control, through steric hindrance or electrostatic repulsion, the differential access of purines to the TMS8-9 domain. Thus, UapA specificity is determined directly by the specific interactions of a given substrate with the TMS8-9 loop and indirectly by interactions of this loop with TMS1 and TMS12. We finally show that intramolecular synergy among UapA domains is highly specific and propose that it forms the basis for the evolution of the unique specificity of UapA for uric acid, a property not present in other NAT members.</style></abstract></record></records></xml>