Summary: R67 dihydrofolate reductase
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R67 dihydrofolate reductase Provide feedback
R67 dihydrofolate reductase is a plasmid encoded enzyme that provides resistance to the antibacterial drug trimethoprim. The R67 dihydrofolate reductase does not share significant similarity to the chromosomal encoded dihydrofolate reductase [1].
Literature references
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Narayana N, Matthews DA, Howell EE, Nguyen-huu X; , Nat Struct Biol 1995;2:1018-1025.: A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site. PUBMED:7583655 EPMC:7583655
External database links
SCOP: | 1vif |
This tab holds annotation information from the InterPro database.
InterPro entry IPR009159
Dihydrofolate reductase (DHFR) ( EC ) 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) [ PUBMED:2830673 ], 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 [ PUBMED:3383852 ].
Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar [ PUBMED:500653 ]. The active site is situated in the N-terminal half of the sequence, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown [ PUBMED:6815178 ] to be involved in the binding of substrate by the enzyme. 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 itself [ PUBMED:2601715 ].
This entry represents a plasmid-encoded DHFR which shows a high level of resistance to the antibiotic trimethoprim. It is a homotetramer with an unusual pore, which contains the active site, passing through the middle of the molecule [ PUBMED:7583655 ]. Its structure is unrelated to that of chromosomal DHFRs.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | dihydrofolate reductase activity (GO:0004146) |
Biological process | response to drug (GO:0042493) |
oxidation-reduction process (GO:0055114) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan ETAP (CL0610), which has the following description:
According to SCOP the domains in this superfamily have an SH3 like barrel fold.
The clan contains the following 4 members:
DHFR_2 FeThRed_A NHase_beta PSI_PsaEAlignments
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Seed (3) |
Full (10) |
Representative proteomes | UniProt (101) |
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RP15 (3) |
RP35 (5) |
RP55 (9) |
RP75 (17) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (3) |
Full (10) |
Representative proteomes | UniProt (101) |
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RP15 (3) |
RP35 (5) |
RP55 (9) |
RP75 (17) |
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Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Curation and family details
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Curation
Seed source: | Pfam-B_27527 (release 9.0) |
Previous IDs: | DHFR; |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Finn RD |
Number in seed: | 3 |
Number in full: | 10 |
Average length of the domain: | 68.40 aa |
Average identity of full alignment: | 47 % |
Average coverage of the sequence by the domain: | 62.01 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 78 | ||||||||||||
Family (HMM) version: | 13 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DHFR_2 domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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