Enzymes
| UniProtKB help_outline | 29,541 proteins |
| Enzyme class help_outline |
|
| GO Molecular Function help_outline |
|
Reaction participants Show >> << Hide
- Name help_outline (6S)-5,6,7,8-tetrahydrofolate Identifier CHEBI:57453 (Beilstein: 10223255) help_outline Charge -2 Formula C19H21N7O6 InChIKeyhelp_outline MSTNYGQPCMXVAQ-RYUDHWBXSA-L SMILEShelp_outline Nc1nc2NC[C@H](CNc3ccc(cc3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)Nc2c(=O)[nH]1 2D coordinates Mol file for the small molecule Search links Involved in 40 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,253 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 7,8-dihydrofolate Identifier CHEBI:57451 Charge -2 Formula C19H19N7O6 InChIKeyhelp_outline OZRNSSUDZOLUSN-LBPRGKRZSA-L SMILEShelp_outline Nc1nc2NCC(CNc3ccc(cc3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)=Nc2c(=O)[nH]1 2D coordinates Mol file for the small molecule Search links Involved in 8 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,247 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:15009 | RHEA:15010 | RHEA:15011 | RHEA:15012 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
|||
| EC numbers help_outline | ||||
| Gene Ontology help_outline | ||||
| KEGG help_outline | ||||
| MetaCyc help_outline | ||||
| EcoCyc help_outline | ||||
| Reactome help_outline | ||||
| M-CSA help_outline |
Publications
-
Regulation of the enzymes involved in the biosynthesis of 2,3-dihydroxybenzoic acid in Aerobacter aerogenes and Escherichia coli.
Young I.G., Gibson F.
Biochim Biophys Acta 177:401-411(1969) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
-
Studies on dihydrofolic reductase. I. Purification and properties of dihydrofolic reductase from chicken liver.
Kaufman B.T., Gardiner R.C.
-
Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate.
Bolin J.T., Filman D.J., Matthews D.A., Hamlin R.C., Kraut J.
X-ray data have been extended to 1.7 A for a binary complex of Escherichia coli dihydrofolate reductase with methotrexate and a ternary complex of Lactobacillus casei dihydrofolate reductase with methotrexate and NADPH. Models for both structures have been refined to R factors of 0.15 and include ... >> More
X-ray data have been extended to 1.7 A for a binary complex of Escherichia coli dihydrofolate reductase with methotrexate and a ternary complex of Lactobacillus casei dihydrofolate reductase with methotrexate and NADPH. Models for both structures have been refined to R factors of 0.15 and include parameters for fixed and liquid solvent. The two species of dihydrofolate reductase resemble one another even more closely than was thought to be the case prior to refinement. Several new structural features have also been discovered. Among them are a cis peptide linking Gly-97 and Gly-98 (L. Casei numbering) in both species, an alpha helix involving residues 43 through 50 in the E. coli enzyme, and the existence of what may be a specific hydration site on exposed alpha helices. Refinement has led to a revised description of the details of methotrexate binding. We now see that a fixed water molecule mediates the interaction between methotrexate's 2-amino group and Thr-116 (L. casei numbering) and that the inhibitor's 4-amino group makes two hydrogen bonds with the enzyme (instead of one). Other revisions are also discussed. A hypothetical model for substrate binding is proposed in which the pteridine ring is turned upside down while all protein and solvent atoms remain fixed. Asp-26 in this model is hydrogen bonded to the substrate's 2-amino group and to N3. << Less
-
The crystal structure of a tetrahydrofolate-bound dihydrofolate reductase reveals the origin of slow product release.
Cao H., Gao M., Zhou H., Skolnick J.
Dihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH. The consensus <i>Escherichia coli</i> DHFR mechanism involves conformational changes between closed and occluded states occurring ... >> More
Dihydrofolate reductase (DHFR) catalyzes the stereospecific reduction of 7,8-dihydrofolate (FH2) to (6s)-5,6,7,8-tetrahydrofolate (FH4) via hydride transfer from NADPH. The consensus <i>Escherichia coli</i> DHFR mechanism involves conformational changes between closed and occluded states occurring during the rate-limiting product release step. Although the Protein Data Bank (PDB) contains over 250 DHFR structures, the FH4 complex structure responsible for rate-limiting product release is unknown. We report to our knowledge the first crystal structure of an <i>E. coli</i>. DHFR:FH4 complex at 1.03 Å resolution showing distinct stabilizing interactions absent in FH2 or related (6R)-5,10-dideaza-FH4 complexes. We discover the time course of decay of the co-purified endogenous FH4 during crystal growth, with conversion from FH4 to FH2 occurring in 2-3 days. We also determine another occluded complex structure of <i>E. coli</i> DHFR with a slow-onset nanomolar inhibitor that contrasts with the methotrexate complex, suggesting a plausible strategy for designing DHFR antibiotics by targeting FH4 product conformations. << Less