Summary: Dihydrofolate reductase
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Dihydrofolate reductase Edit Wikipedia article
Crystal structure of chicken liver dihydrofolate reductase. PDB entry
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|R67 dihydrofolate reductase|
High-resolution structure of a plasmid-encoded dihydrofolate reductase from E.coli. PDB entry
Ribbon diagram of human dihydrofolate reductase in complex with folate (blue). From .
|Symbols||; DHFRP1; DYR|
|External IDs||ChEMBL: GeneCards:|
Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the DHFR gene. It is found in the q11→q22 region of chromosome 5. Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar.
A central eight-stranded beta-pleated sheet makes up the main feature of the polypeptide backbone folding of DHFR. Seven of these strands are parallel and the eighth runs antiparallel. Four alpha helices connect successive beta strands. Residues 9 – 24 are termed "Met20" or "loop 1" and, along with other loops, are part of the major subdomain that surround the active site. 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 to be involved in the binding of substrate by the enzyme.
Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes.
Found in all organisms, DHFR has a critical role in regulating the amount of tetrahydrofolate in the cell. Tetrahydrofolate and its derivatives are essential for purine and thymidylate synthesis, which are important for cell proliferation and cell growth. DHFR plays a central role in the synthesis of nucleic acid precursors, and it has been shown that mutant cells that completely lack DHFR require glycine, an amino acid, and thymidine to grow. DHFR has also been demonstrated as an enzyme involved in the salvage of tetrahydrobiopterin from dihydrobiopterin
DHFR catalyzes the transfer of a hydride from NADPH to dihydrofolate with an accompanying protonation to produce tetrahydrofolate. In the end, dihydrofolate is reduced to tetrahydrofolate and NADPH is oxidized to NADP+. The high flexibility of Met20 and other loops near the active site play a role in promoting the release of the product, tetrahydrofolate. In particular the Met20 loop helps stabilize the nicotinamide ring of the NADPH to promote the transfer of the hydride from NADPH to dihydrofolate.
Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Treatment is with reduced forms of folic acid. Because tetrahydrofolate, the product of this reaction, is the active form of folate in humans, inhibition of DHFR can cause functional folate deficiency. DHFR is an attractive pharmaceutical target for inhibition due to its pivotal role in DNA precursor synthesis. Trimethoprim, an antibiotic, inhibits bacterial DHFR while methotrexate, a chemotherapy agent, inhibits mammalian DHFR. However, resistance has developed against some drugs, as a result of mutational changes in DHFR itself.
Since folate is needed by rapidly dividing cells to make thymine, this effect may be used to therapeutic advantage.
DHFR can be targeted in the treatment of cancer. DHFR is responsible for the levels of tetrahydrofolate in a cell, and the inhibition of DHFR can limit the growth and proliferation of cells that are characteristic of cancer. Methotrexate, a competitive inhibitor of DHFR, is one such anticancer drug that inhibits DHFR. Other drugs include trimethoprim and pyrimethamine. These three are widely used as antitumor and antimicrobial agents.
Trimethoprim has shown to have activity against a variety of Gram-positive bacterial pathogens. However, resistance to trimethoprim and other drugs aimed at DHFR can arise due to a variety of mechanisms, limiting the success of their therapeutical uses. Resistance can arise from DHFR gene amplification, mutations in DHFR, decrease in the uptake of the drugs, among others. Regardless, trimethoprim and sulfamethoxazole in combination has been used as an antibacterial agent for decades.
Folic acid is necessary for growth, and the pathway of the metabolism of folic acid is a target in developing treatments for cancer. DHFR is one such target. A regimen of fluorouracil, doxorubicin, and methotrexate was shown to prolong survival in patients with advanced gastric cancer. Further studies into inhibitors of DHFR can lead to more ways to treat cancer.
Bacteria also need DHFR to grow and multiply and hence inhibitors selective for bacterial DHFR have found application as antibacterial agents.
Potential anthrax treatment
Dihydrofolate reductase from Bacillus anthracis (BaDHFR) a validated drug target in the treatment of the infectious disease, anthrax. BaDHFR is less sensitive to trimethoprim analogs than is dihydrofolate reductase from other species such as Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. A structural alignment of dihydrofolate reductase from all four species shows that only BaDHFR has the combination phenylalanine and tyrosine in positions 96 and 102, respectively.
BaDHFR's resistance to trimethoprim analogs is due to these two residues (F96 and Y102), which also confer improved kinetics and catalytic efficiency. Current research uses active site mutants in BaDHFR to guide lead optimization for new antifolate inhibitors.
As a research tool
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".
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- Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, Nienhuis AW (March 1984). "The functional human dihydrofolate reductase gene". J. Biol. Chem. 259 (6): 3933–43. PMID 6323448.
- Funanage VL, Myoda TT, Moses PA, Cowell HR (October 1984). "Assignment of the human dihydrofolate reductase gene to the q11----q22 region of chromosome 5". Mol. Cell. Biol. 4 (10): 2010–6. PMC 369017. PMID 6504041.
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- Matthews DA, Alden RA, Bolin JT, Freer ST, Hamlin R, Xuong N, Kraut J, Poe M, Williams M, Hoogsteen K (July 1977). "Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate". Science 197 (4302): 452–5. doi:10.1126/science.17920. PMID 17920.
- Filman DJ, Bolin JT, Matthews DA, Kraut J (November 1982). "Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. II. Environment of bound NADPH and implications for catalysis". J. Biol. Chem. 257 (22): 13663–72. PMID 6815179.
- Osborne MJ, Schnell J, Benkovic SJ, Dyson HJ, Wright PE (August 2001). "Backbone dynamics in dihydrofolate reductase complexes: role of loop flexibility in the catalytic mechanism". Biochemistry 40 (33): 9846–59. doi:10.1021/bi010621k. PMID 11502178.
- Bolin JT, Filman DJ, Matthews DA, Hamlin RC, Kraut J (November 1982). "Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate". J. Biol. Chem. 257 (22): 13650–62. PMID 6815178.
- "Entrez Gene: DHFR dihydrofolate reductase".
- Schnell JR, Dyson HJ, Wright PE (2004). "Structure, dynamics, and catalytic function of dihydrofolate reductase". Annu Rev Biophys Biomol Struct 33 (1): 119–40. doi:10.1146/annurev.biophys.33.110502.133613. PMID 15139807.
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- Crabtree MJ, Tatham AL, Hale AB, Alp NJ, Channon KM (2009). "Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways". J. Biol. Chem. 284 (41): 28128–36. doi:10.1074/jbc.M109.041483. PMC 2788863. PMID 19666465.
- Cowman AF, Lew AM (November 1989). "Antifolate drug selection results in duplication and rearrangement of chromosome 7 in Plasmodium chabaudi". Mol. Cell. Biol. 9 (11): 5182–8. PMC 363670. PMID 2601715.
- Li R, Sirawaraporn R, Chitnumsub P, Sirawaraporn W, Wooden J, Athappilly F, Turley S, Hol WG (January 2000). "Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs". J. Mol. Biol. 295 (2): 307–23. doi:10.1006/jmbi.1999.3328. PMID 10623528.
- Benkovic SJ, Fierke CA, Naylor AM (March 1988). "Insights into enzyme function from studies on mutants of dihydrofolate reductase". Science 239 (4844): 1105–10. doi:10.1126/science.3125607. PMID 3125607.
- Hawser S, Lociuro S, Islam K (March 2006). "Dihydrofolate reductase inhibitors as antibacterial agents". Biochem. Pharmacol. 71 (7): 941–8. doi:10.1016/j.bcp.2005.10.052. PMID 16359642.
- Narayana N, Matthews DA, Howell EE, Nguyen-huu X (November 1995). "A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site". Nat. Struct. Biol. 2 (11): 1018–25. doi:10.1038/nsb1195-1018. PMID 7583655.
- Huennekens FM (June 1996). "In search of dihydrofolate reductase". Protein Sci. 5 (6): 1201–8. doi:10.1002/pro.5560050626. PMC 2143423. PMID 8762155.
- Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR (July 2002). "Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase". Biochim. Biophys. Acta 1587 (2–3): 164–73. doi:10.1016/S0925-4439(02)00079-0. PMID 12084458.
- Bailey SW, Ayling JE (2009). "The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake". Proc. Natl. Acad. Sci. U.S.A. 106 (36): 15424–9. doi:10.1073/pnas.0902072106. PMC 2730961. PMID 19706381.
- Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (July 1993). "Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer". Cancer 72 (1): 37–41. doi:10.1002/1097-0142(19930701)72:1<37::AID-CNCR2820720109>3.0.CO;2-P. PMID 8508427.
- Srinivasan B and Skolnick J (2015). "Insights into the slow-onset tight-binding inhibition of Escherichia coli dihydrofolate reductase: detailed mechanistic characterization of pyrrolo [3,2-f] quinazoline-1,3-diamine and its derivatives as novel tight-binding inhibitors.". FEBS J 282 (10): 1922–1938. doi:10.1111/febs.13244. PMID 25703118.
- Srinivasan B, Tonddast-Navaei S and Skolnick J (2015). "Ligand binding studies, preliminary structure-activity relationship and detailed mechanistic characterization of 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine derivatives as inhibitors of Escherichia coli dihydrofolate reductase.". Eur J Med Chem. 103: 600–614. doi:10.1016/j.ejmech.2015.08.021. PMID 26414808.
- Beierlein JM, Karri NG, Anderson AC (October 2010). "Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships". J. Med. Chem. 53 (20): 7327–36. doi:10.1021/jm100727t. PMC 3618964. PMID 20882962.
- Mayhew M, da Silva AC, Martin J, Erdjument-Bromage H, Tempst P, Hartl FU (February 1996). "Protein folding in the central cavity of the GroEL-GroES chaperonin complex". Nature 379 (6564): 420–6. doi:10.1038/379420a0. PMID 8559246.
- Maguire M, Nield PC, Devling T, Jenkins RE, Park BK, Polański R, Vlatković N, Boyd MT (May 2008). "MDM2 regulates dihydrofolate reductase activity through monoubiquitination". Cancer Res. 68 (9): 3232–42. doi:10.1158/0008-5472.CAN-07-5271. PMC 3536468. PMID 18451149.
- Joska TM, Anderson AC (October 2006). "Structure-activity relationships of Bacillus cereus and Bacillus anthracis dihydrofolate reductase: toward the identification of new potent drug leads". Antimicrob. Agents Chemother. 50 (10): 3435–43. doi:10.1128/AAC.00386-06. PMC 1610094. PMID 17005826.
- Chan DC, Fu H, Forsch RA, Queener SF, Rosowsky A (June 2005). "Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with omega-carboxyalkoxy or omega-carboxy-1-alkynyl substitution in the side chain". J. Med. Chem. 48 (13): 4420–31. doi:10.1021/jm0581718. PMID 15974594.
- Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR (2002). "Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase". Biochim. Biophys. Acta 1587 (2–3): 164–73. doi:10.1016/S0925-4439(02)00079-0. PMID 12084458.
- Stockman BJ, Nirmala NR, Wagner G, Delcamp TJ, DeYarman MT, Freisheim JH (1992). "Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution". Biochemistry 31 (1): 218–29. doi:10.1021/bi00116a031. PMID 1731871.
- Beltzer JP, Spiess M (1991). "In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles". EMBO J. 10 (12): 3735–42. PMC 453108. PMID 1935897.
- Davies JF, Delcamp TJ, Prendergast NJ, Ashford VA, Freisheim JH, Kraut J (1990). "Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate". Biochemistry 29 (40): 9467–79. doi:10.1021/bi00492a021. PMID 2248959.
- Will CL, Dolnick BJ (1989). "5-Fluorouracil inhibits dihydrofolate reductase precursor mRNA processing and/or nuclear mRNA stability in methotrexate-resistant KB cells". J. Biol. Chem. 264 (35): 21413–21. PMID 2592384.
- Masters JN, Attardi G (1985). "Discrete human dihydrofolate reductase gene transcripts present in polysomal RNA map with their 5' ends several hundred nucleotides upstream of the main mRNA start site". Mol. Cell. Biol. 5 (3): 493–500. PMC 366741. PMID 2859520.
- Miszta H, Dabrowski Z, Lanotte M (1988). "In vitro patterns of enzymic tetrahydrofolate dehydrogenase (EC 22.214.171.124) expression in bone marrow stromal cells". Leukemia 2 (11): 754–9. PMID 3185016.
- Oefner C, D'Arcy A, Winkler FK (1988). "Crystal structure of human dihydrofolate reductase complexed with folate". Eur. J. Biochem. 174 (2): 377–85. doi:10.1111/j.1432-1033.1988.tb14108.x. PMID 3383852.
- Yang JK, Masters JN, Attardi G (1984). "Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes". J. Mol. Biol. 176 (2): 169–87. doi:10.1016/0022-2836(84)90419-4. PMID 6235374.
- Masters JN, Yang JK, Cellini A, Attardi G (1983). "A human dihydrofolate reductase pseudogene and its relationship to the multiple forms of specific messenger RNA". J. Mol. Biol. 167 (1): 23–36. doi:10.1016/S0022-2836(83)80032-1. PMID 6306253.
- Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, Nienhuis AW (1984). "The functional human dihydrofolate reductase gene". J. Biol. Chem. 259 (6): 3933–43. PMID 6323448.
- Funanage VL, Myoda TT, Moses PA, Cowell HR (1984). "Assignment of the human dihydrofolate reductase gene to the q11----q22 region of chromosome 5". Mol. Cell. Biol. 4 (10): 2010–6. PMC 369017. PMID 6504041.
- Masters JN, Attardi G (1983). "The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase". Gene 21 (1–2): 59–63. doi:10.1016/0378-1119(83)90147-6. PMID 6687716.
- Morandi C, Masters JN, Mottes M, Attardi G (1982). "Multiple forms of human dihydrofolate reductase messenger RNA. Cloning and expression in Escherichia coli of their DNA coding sequence". J. Mol. Biol. 156 (3): 583–607. doi:10.1016/0022-2836(82)90268-6. PMID 6750132.
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- Mayhew M, da Silva AC, Martin J, Erdjument-Bromage H, Tempst P, Hartl FU (1996). "Protein folding in the central cavity of the GroEL-GroES chaperonin complex". Nature 379 (6564): 420–6. doi:10.1038/379420a0. PMID 8559246.
- Gross M, Robinson CV, Mayhew M, Hartl FU, Radford SE (1996). "Significant hydrogen exchange protection in GroEL-bound DHFR is maintained during iterative rounds of substrate cycling". Protein Sci. 5 (12): 2506–13. doi:10.1002/pro.5560051213. PMC 2143321. PMID 8976559.
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- Cody V, Galitsky N, Luft JR, Pangborn W, Rosowsky A, Blakley RL (1997). "Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523". Biochemistry 36 (45): 13897–903. doi:10.1021/bi971711l. PMID 9374868.
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This tab holds annotation information from the InterPro database.
InterPro entry IPR001796
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].
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||nucleotide biosynthetic process (GO:0009165)|
|oxidation-reduction process (GO:0055114)|
|glycine biosynthetic process (GO:0006545)|
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|Author:||Finn RD, Griffiths-Jones SR|
|Number in seed:||60|
|Number in full:||1734|
|Average length of the domain:||160.20 aa|
|Average identity of full alignment:||31 %|
|Average coverage of the sequence by the domain:||78.32 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
|Download:||download the raw HMM for this family|
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In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 4 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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_1 domain has been found. There are 553 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 seqence.
Loading structure mapping...