5j4n
Crystal structure of the L-arginine/agmatine antiporter AdiC in complex with agmatine at 2.6 Angstroem resolution
Structural highlights
FunctionADIC_ECOLI Major component of the acid-resistance (AR) system allowing enteric pathogens to survive the acidic environment in the stomach (Probable). Exchanges extracellular arginine for its intracellular decarboxylation product agmatine (Agm) thereby expelling intracellular protons (PubMed:12867448, PubMed:14594828, PubMed:19578361, PubMed:21368142). Probably undergoes several conformational states in order to translocate the substrate across the membrane; keeps the substrate accessible to only 1 side of the membrane at a time by opening and closing 3 membrane-internal gates (Probable).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedPathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-A and 2.2-A resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli. Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.,Ilgu H, Jeckelmann JM, Gapsys V, Ucurum Z, de Groot BL, Fotiadis D Proc Natl Acad Sci U S A. 2016 Aug 31. pii: 201605442. PMID:27582465[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
