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Dihydrofolate Reductase: X-ray Structure of the Binary Complex with Methotrexate
Abstract
A central eight-stranded β-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N (1) , N (8) , and the 2-amino group of methotrexate.
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Cited by
The Anatomy and Taxonomy of Protein Structure
Richardson, J. S. (1981) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60520-3 · Cited by 3,375
Dauber‐Osguthorpe, P., Roberts, V. A., Osguthorpe, D. J., Wolff, J., Genest, M., & Hagler, A. T. (1988) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.340040106 · Cited by 2,083
Extensive impact of non-antibiotic drugs on human gut bacteria
Maier, L., Pruteanu, M., Kuhn, M., Zeller, G., Telzerow, A., Anderson, E. E., Brochado, A. R., Fernandez, K. C., Dose, H., Mori, H., et al. (2018) · Nature · doi:10.1038/nature25979 · Cited by 1,905
Structure-Based Strategies for Drug Design and Discovery
Kuntz, I. D. (1992) · Science · doi:10.1126/science.257.5073.1078 · Cited by 989
Evolutionary paths to antibiotic resistance under dynamically sustained drug selection
Toprak, E., Veres, A., Michel, J.-B., Chait, R., Hartl, D. L., & Kishony, R. (2012) · Nature Genetics · doi:10.1038/ng.1034 · Cited by 764
Metadata
- Authors
- Matthews, D. A., Alden, R. A., Bolin, J. T., Freer, S. T., Hamlin, R., Xuong, N., Kraut, J., Poe, M., Williams, M., & Hoogsteen, K.
- Venue
- Science
- Published
- 1977-07-29
- Volume
- 197
- Issue
- 4302
- Pages
- 452-455
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2055009933
- Cited by
- 322
- References
- 0
- FWCI
- 21.06
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Dihydrofolate Reductase: X-ray Structure of the Binary Complex with Methotrexate. https://app.cochat.ai/papers/10.1126/science.17920
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- Matthews, D. A., Alden, R. A., Bolin, J. T., Freer, S. T., Hamlin, R., Xuong, N., Kraut, J., Poe, M., Williams, M., & Hoogsteen, K. (1977). Dihydrofolate Reductase: X-ray Structure of the Binary Complex with Methotrexate. Science. https://doi.org/10.1126/science.17920
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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