Editing Dihydrofolate reductase (section)

==== Potential anthrax treatment ====
[[File:Structural alignment of ba sa ec sp dhfr.png|thumb|class=skin-invert-image|[[Structural alignment]] of chromosomal (Type I) dihydrofolate reductase from ''Bacillus anthracis'' (BaDHFR), ''Staphylococcus aureus'' (SaDHFR), ''Escherichia coli'' (EcDHFR), and ''Streptococcus pneumoniae'' (SpDHFR)]]

Dihydrofolate reductase from ''[[Bacillus anthracis]]'' (BaDHFR) is a validated drug target in the treatment of the infectious disease, anthrax. BaDHFR is less sensitive to [[trimethoprim]] analogs than is dihydrofolate reductase from other species such as ''[[Escherichia coli]]'', ''[[Staphylococcus aureus]]'', and ''[[Streptococcus pneumoniae]]''. A structural alignment of dihydrofolate reductase from all four species shows that only BaDHFR has the combination [[phenylalanine]] and [[tyrosine]] in positions 96 and 102, respectively.

BaDHFR's resistance to [[trimethoprim]] analogs is due to these two residues (F96 and Y102), which also confer improved kinetics and catalytic efficiency.<ref name="pmid20882962">{{cite journal | vauthors = Beierlein JM, Karri NG, Anderson AC | title = Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 20 | pages = 7327–36 | date = October 2010 | pmid = 20882962 | pmc = 3618964 | doi = 10.1021/jm100727t }}</ref> Current research uses active site mutants in BaDHFR to guide lead optimization for new antifolate inhibitors.<ref name="pmid20882962"/>