The AbgT family: A novel class of antimetabolite transporters.
The AbgT family of transporters was thought to contribute to bacterial folate biosynthesis by importing the catabolite p-aminobenzoyl-glutamate for producing this essential vitamin. Approximately 13,000 putative transporters of the family have been identified. However, before our work, no structural information was available and even functional data were minimal for this family of membrane proteins. To elucidate the structure and function of the AbgT family of transporters, we recently determined the X-ray structures of the full-length Alcanivorax borkumensis YdaH and Neisseria gonorrhoeae MtrF membrane proteins. The structures reveal that these two transporters assemble as dimers with architectures distinct from all other families of transporters. Both YdaH and MtrF are bowl-shaped dimers with a solvent-filled basin extending from the cytoplasm halfway across the membrane bilayer. The protomers of YdaH and MtrF contain nine transmembrane helices and two hairpins. These structures directly suggest a plausible pathway for substrate transport. A combination of the crystal structure, genetic analysis and substrate accumulation assay indicates that both YdaH and MtrF behave as exporters, capable of removing the folate metabolite p-aminobenzoic acid from bacterial cells. Further experimental data based on drug susceptibility and radioactive transport assay suggest that both YdaH and MtrF participate as antibiotic efflux pumps, importantly mediating bacterial resistance to sulfonamide antimetabolite drugs. It is possible that many of these AbgT-family transporters act as exporters, thereby conferring bacterial resistance to sulfonamides. The AbgT-family transporters may be important targets for the rational design of novel antibiotics to combat bacterial infections.
['Delmar|Jared A|JA|', 'Yu|Edward W|EW|']
D000595:Amino Acid Sequence D000900:Anti-Bacterial Agents D000963:Antimetabolites D001419:Bacteria D001426:Bacterial Proteins D001692:Biological Transport D018360:Crystallography, X-Ray D005492:Folic Acid D015964:Gene Expression Regulation, Bacterial D026901:Membrane Transport Proteins D008958:Models, Molecular D008969:Molecular Sequence Data D011487:Protein Conformation D016415:Sequence Alignment
antimetabolite transporters membrane proteins Alcanivorax borkumensis YdaH Neisseria gonorrhoeae MtrF AbgT-family transporters X-ray crystallography