DOI: 10.1111/j.1432-1033.1988.tb14108.x. Crystal structure of human dihydrofolate reductase complexed with folate

Crystal structure of human dihydrofolate reductase complexed with folate

10.1111/j.1432-1033.1988.tb14108.x

Crossref journal-article

Wiley

European Journal of Biochemistry (311)

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, 178–1841. 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].

Bibliography

OEFNER, C., DâARCY, A., & WINKLER, F. K. (1988). Crystal structure of human dihydrofolate reductase complexed with folate. European Journal of Biochemistry, 174(2), 377â385. Portico.

Authors 3

Christian OEFNER (first)
Allan D'ARCY (additional)
Fritz K. WINKLER (additional)

References 28 Referenced 171

{'key': 'e_1_2_3_2_2', 'first-page': '191', 'volume-title': 'Folates and pterins ‐ Chemistry and biochemistry of folates', 'author': 'Blakley R. L.', 'year': '1984'} / Folates and pterins ‐ Chemistry and biochemistry of folates by Blakley R. L. (1984)
10.1016/S0021-9258(18)89744-7
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{'key': 'e_1_2_3_5_2', 'first-page': '839', 'volume-title': 'Chemistry and biology of pteridines', 'author': 'Stüber D.', 'year': '1986'} / Chemistry and biology of pteridines by Stüber D. (1986)
10.1107/S0567740875002695 / Acta Crystallogr. by Tickle I. J. (1975)
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{'key': 'e_1_2_3_16_2', 'first-page': '249', 'volume': '38', 'author': 'Müller K.', 'year': '1984', 'journal-title': 'Chimia'} / Chimia by Müller K. (1984)
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{'key': 'e_1_2_3_19_2', 'first-page': '969', 'volume-title': 'Chemistry and Biology of pteridines', 'author': 'Sutton P. A.', 'year': '1986'} / Chemistry and Biology of pteridines by Sutton P. A. (1986)
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10.1126/science.3511529
Matthews D. A. Smith S. L. Baccanari D. P.&Burchall J. J.(1986)Biochemistry 2.5 4194–4204. (10.1021/bi00363a005)
{'key': 'e_1_2_3_25_2', 'first-page': '37', 'volume-title': 'Advances in pharmacology and chemotherapy', 'author': 'Gready J. E.', 'year': '1980'} / Advances in pharmacology and chemotherapy by Gready J. E. (1980)
10.1021/bi00263a034
{'key': 'e_1_2_3_27_2', 'first-page': '435', 'volume-title': 'Chemistry and biology of pteridines', 'author': 'Matthews D. A.', 'year': '1983'} / Chemistry and biology of pteridines by Matthews D. A. (1983)
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10.1021/jm00344a018

Dates

Type	When
Created	20 years, 5 months ago (March 3, 2005, 9:15 p.m.)
Deposited	1 year, 8 months ago (Nov. 23, 2023, 3:59 a.m.)
Indexed	2 months, 2 weeks ago (June 6, 2025, 5:08 a.m.)
Issued	37 years, 2 months ago (June 1, 1988)
Published	37 years, 2 months ago (June 1, 1988)
Published Online	20 years, 5 months ago (March 3, 2005)
Published Print	37 years, 2 months ago (June 1, 1988)

Funders 0

None

BibTeX

@article{OEFNER_1988, title={Crystal structure of human dihydrofolate reductase complexed with folate}, volume={174}, ISSN={1432-1033}, url={http://dx.doi.org/10.1111/j.1432-1033.1988.tb14108.x}, DOI={10.1111/j.1432-1033.1988.tb14108.x}, number={2}, journal={European Journal of Biochemistry}, publisher={Wiley}, author={OEFNER, Christian and D’ARCY, Allan and WINKLER, Fritz K.}, year={1988}, month=jun, pages={377–385} }

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