To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS. To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017. From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...] View this page in https
Dihydrofolate reductases (DHFRs) (EC 18.104.22.168)  are ubiquitous enzymes which
catalyze the NADPH-linked reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. DHFRs are also capable of catalyzing the NADPH-linked
reduction of folate to 7,8-dihydrofolate, but at a lesser rate, which varies
among species. They can be inhibited by a number of antagonists such as
trimethroprim and methotrexate which are used as antibacterial or
Thymidylate synthase (TS) (see <PDOC00086>) and DHFR catalyze sequential
reactions in the thymidylate cycle, which supplies cells with their sole de
novo source of 2'-deoxythymidylate (dTMP) for DNA synthesis. TS catalyzes a
reductive methylation of 2'deoxyuridylate (dUMP) to form dTMP in which the
cofactor for the reaction, 5,10-methylenetetrahydrofolate is converted to
dihydrofolate (FH(2)). DHFR then reduces FH(2) to tetrahydrofolate (FH(4)) in
a reaction requiring NADPH. In sources as diverse as bacteriophage,
prokaryotes, fungi, mammalian viruses, and vertebrates, TS and DHFR are
distinct monofunctional enzymes. Protozoa and at least some plants are unusual
in having a joined bifunctional polypetide that catalyzes both reactions
An eight-stranded β sheet consisting of seven parallel strands and a
carboxy-terminal antiparallel strand composes the core of the DHFR domain. The
β-sheet core is flanked by α-helices (see <PDB:1DRH>) [2,3,4,5,6].
We have derived a signature pattern from a region in the N-terminal part of
the DHFR domain, which includes a conserved Pro-Trp dipeptide; the tryptophan
has been shown  to be involved in the binding of substrate by the enzyme.
We have also developed a profile, which covers the entire DHFR domain.
September 2007 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
Harpers' Review of Biochemistry, Lange, Los Altos (1985).
Knighton D.R., Kan C.-C., Howland E., Janson C.A., Hostomska Z., Welsh K.M., Matthews D.A.
Structure of and kinetic channelling in bifunctional dihydrofolate reductase-thymidylate synthase.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.