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The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery
Author(s) -
Bermingham Alun,
Derrick Jeremy P.
Publication year - 2002
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.10114
Subject(s) - enzyme , biosynthesis , antibiotics , drug , drug discovery , folic acid , biochemistry , metabolic pathway , biology , gtp' , bacteria , folic acid antagonists , computational biology , chemistry , pharmacology , medicine , genetics
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. BioEssays 24:637–648, 2002. © 2002 Wiley Periodicals, Inc.