4dfr
CRYSTAL STRUCTURES OF ESCHERICHIA COLI AND LACTOBACILLUS CASEI DIHYDROFOLATE REDUCTASE REFINED AT 1.7 ANGSTROMS RESOLUTION. I. GENERAL FEATURES AND BINDING OF METHOTREXATE
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OverviewOverview
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.
About this StructureAbout this Structure
4DFR is a Single protein structure of sequence from Escherichia coli b with CL, CA and MTX as ligands. This structure superseeds the now removed PDB entry 2DFR. Active as Dihydrofolate reductase, with EC number 1.5.1.3 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate., Bolin JT, Filman DJ, Matthews DA, Hamlin RC, Kraut J, J Biol Chem. 1982 Nov 25;257(22):13650-62. PMID:6815178
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