Development of a yeast assay for rapid screening of inhibitors of human-derived Pneumocystis carinii dihydrofolate reductase.
Human-derived Pneumocystis carinii dihydrofolate reductase (DHFR) was expressed in a Saccharomyces cerevisiae strain whose growth depends on complementation by this enzyme. We utilized a quantitative assay to measure the sensitivity of this yeast strain to DHFR inhibitors. This assay should be useful for identifying new inhibitors of human-derived P. carinii DHFR.
Ma
Liang
L
Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662, USA.
Jia
Qiuyao
Q
Kovacs
Joseph A
JA
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D011010:Pneumocystis / Q000201:enzymology*; D016720:Pneumocystis Infections / Q000201:enzymology / Q000382:microbiology; D011739:Pyrimethamine / Q000494:pharmacology; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology; D014295:Trimethoprim / Q000494:pharmacology; D016597:Trimetrexate / Q000494:pharmacology
D005493:Folic Acid Antagonists; D014227:Triazines; C006201:BRL 6231; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase; D016597:Trimetrexate; D011739:Pyrimethamine