cd00209

DHFR

CDD entry
Member databaseCDD
CDD typedomain
Short nameDHFR
SetDHFR

Description

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.
[4, 2, 1, 3, 5, 7, 6]

References

1.Eukaryotic dihydrofolate reductase. Blakley RL. Adv Enzymol Relat Areas Mol Biol 70, 23-102, (1995). PMID: 8638484

2.Structure-activity relationships of dihydrofolate reductase inhibitors. Bowden K, Harris NV, Watson CA. J Chemother 5, 377-88, (1993). PMID: 8195829

3.Evolution of the bacterial dihydrofolate reductase inhibitors. Periti P. J Antimicrob Chemother 36, 887-90, (1995). PMID: 8821588

4.Molecular aspects and mechanism of action of dihydrofolate reductase inhibitors. Hartman PG. J Chemother 5, 369-76, (1993). PMID: 8195828

5.Insights into antifolate resistance from malarial DHFR-TS structures. Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, Vanichtanankul J, Sirawaraporn W, Taylor P, Walkinshaw MD, Yuthavong Y. Nat. Struct. Biol. 10, 357-65, (2003). View articlePMID: 12704428

6.Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. Cody V, Luft JR, Pangborn W, Gangjee A, Queener SF. Acta Crystallogr. D Biol. Crystallogr. 60, 646-55, (2004). View articlePMID: 15039552

7.Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase. O'Neil RH, Lilien RH, Donald BR, Stroud RM, Anderson AC. J. Biol. Chem. 278, 52980-7, (2003). View articlePMID: 14555647

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