The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery.
The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs. Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined. Given that structure-based drug design strategies are now widely employed, these recent developments have prompted a re-evaluation of the potential of each of the enzymes in the pathway as a target for development of specific inhibitors. Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention.
Department of Biomolecular Sciences, UMIST, Manchester, UK.
Alun
A
Bermingham
Jeremy P
JP
Derrick
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005492:Folic Acid / Q000096:biosynthesis*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D020836:Protein Structure, Quaternary
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005492:Folic Acid