1DRF

CRYSTAL STRUCTURE OF HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH FOLATE

Summary for 1DRF

• Entry DOI: 10.2210/pdb1drf/pdb
• Descriptor: DIHYDROFOLATE REDUCTASE, SULFATE ION, FOLIC ACID, ... (4 entities in total)
• Functional Keywords: oxidoreductase (ch-nh(d)-nad or nadp(a))
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 21983.05

Authors

Oefner, C.,D'Arcy, A.,Winkler, F.K. (deposition date: 1990-08-09, release date: 1992-01-15, Last modification date: 2024-02-07)

Primary citation

Oefner, C.,D'Arcy, A.,Winkler, F.K.
Crystal structure of human dihydrofolate reductase complexed with folate.
Eur.J.Biochem., 174:377-385, 1988

PubMed Abstract: The crystal structure of recombinant human dihydrofolate reductase with folate bound in the active site has been determined and the structural model refined at 0.2-nm resolution. Preliminary studies of the binding of the inhibitors methotrexate and trimethoprim to the human apoenzyme have been performed at 0.35-nm resolution. The conformations of the chemically very similar ligands folate and methotrexate, one a substrate the other a potent inhibitor, differ substantially in that their pteridine rings are in inverse orientations relative to their p-aminobenzoyl-L-glutamate moieties. Methotrexate binding is similar to that previously observed in two bacterial enzymes but is quite different from that observed in the enzyme from a mouse lymphoma cell line [Stammers et al. (1987) FEBS Lett. 218, 178-184]. The geometry of the polypeptide chain around the folate binding site in the human enzyme is not consistent with conclusions previously drawn with regard to the species selectivity of the inhibitor trimethoprim [Matthews et al. (1985) J. Biol. Chem. 260, 392-399].

PubMed: 3383852
DOI: 10.1111/j.1432-1033.1988.tb14108.x

Experimental method

X-RAY DIFFRACTION (2 Å)