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A gene for dihydrofolate reductase in a herpesvirus.
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Crystal structure of human dihydrofolate reductase complexed with folate.
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Porcine liver dihydrofolate reductase.
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Antifolate drug selection results in duplication and rearrangement of
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Dihydrofolate reductase (DHFR) catalyses the NADPH-dependent reduction of
dihydrofolate to tetrahydrofolate, an essential step in de novo synthesis
both of glycine and of purines and deoxythymidine phosphate (the precursors
of DNA synthesis) , and important also in the conversion of deoxyuridine
monophosphate to deoxythymidine monophosphate. Although DHFR is found
ubiquitously in prokaryotes and eukaryotes, and is found in all dividing
cells, maintaining levels of fully reduced folate coenzymes, the catabolic
steps are still not well understood .
Bacterial species possesses distinct DHFR enzymes (based on their pattern
of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly
similar . The active site is situated in the N-terminal half of the
sequence, which is the area of least variability. Its central role in DNA
precursor synthesis, coupled with its inhibition by antagonists such as
trimethoprim and methotrexate, which are used as anti-bacterial or anti-
cancer agents, has made DHFR a target of anticancer chemotherapy. However,
resistance has developed against some drugs, as a result of changes in DHFR
DHFR is a 4-element fingerprint that provides a signature for DHFRs. The
fingerprint was derived from an initial alignment of 11 sequences: the
motifs line the active site, motif 1 including the region encoded by
PROSITE pattern DHFR (PS00075), in which the conserved Trp is implicated
in substrate binding. Two iterations on OWL21.1 were required to reach
convergence, at which point a true set comprising 55 sequences was
identified. Nine partial matches were also found, all of which are
An update on SPTR37_9f identified a true set of 77 sequences, and 9