DOI: 10.1002/prot.340110405. Changes in the electron density of the cofactor NADPH on binding to <i>E. coli</i> dihydrofolate reductase

Changes in the electron density of the cofactor NADPH on binding to E. coli dihydrofolate reductase

10.1002/prot.340110405

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractQuantum‐mechanical electron density calculations reveal that a significant polarization is induced in the cofactor NADPH (reduced nicotinamide adenine dinucleotide phosphate) on binding to the enzyme dihydrofolate reductase. The calculations indicate that electron density corresponding to ∼0.7 electron charges is shifted within the molecule, extending over more than 20Å. Further calculations on proposed enzyme mutants show that the polarization of NADPH on binding to DHFR is, in large part, induced by a motif of three positively charged residues. This motif was also identified to be directly responsible for the positive electrostatic potential surrounding the cofactor binding site in the enzyme. The possibility of this long‐range polarization of NADPH was originally proposed based on a previous study of ligand binding to DHFR where a conserved structural motif of three positively charged residues was found to play a major role in polarizing the substrate folate over its entire length of 18 Å.

Bibliography

Bajorath, J., Li, Z., Fitzgerald, G., Kitson, D. H., Farnum, M., Fine, R. M., Kraut, J., & Hagler, A. T. (1991). Changes in the electron density of the cofactor NADPH on binding to E. coli dihydrofolate reductase. Proteins: Structure, Function, and Bioinformatics, 11(4), 263â270. Portico.

Authors 8

Jürgen Bajorath (first)
Zhenqin Li (additional)
George Fitzgerald (additional)
David H. Kitson (additional)
Martin Farnum (additional)
Richard M. Fine (additional)
Joseph Kraut (additional)
Arnold T. Hagler (additional)

References 41 Referenced 15

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10.1016/S0021-9258(18)89743-5
10.1016/S0021-9258(18)33498-7 / J. Biol. Chem. / Crystal strutures of Escherichia coli and Lactobacillus casei dihydrofolate reductase at 1.7 Å resolution. II. Environment of bound NADPH and implications for catalysis by Filman D. J. (1982)
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Dates

Type	When
Created	20 years, 2 months ago (May 28, 2005, 9:13 p.m.)
Deposited	1 year, 10 months ago (Oct. 23, 2023, 3:43 a.m.)
Indexed	2 months, 2 weeks ago (June 6, 2025, 5:08 a.m.)
Issued	33 years, 8 months ago (Dec. 1, 1991)
Published	33 years, 8 months ago (Dec. 1, 1991)
Published Online	21 years, 6 months ago (Feb. 3, 2004)
Published Print	33 years, 8 months ago (Dec. 1, 1991)

Funders 0

None

BibTeX

@article{Bajorath_1991, title={Changes in the electron density of the cofactor NADPH on binding to E. coli dihydrofolate reductase}, volume={11}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.340110405}, DOI={10.1002/prot.340110405}, number={4}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Bajorath, Jürgen and Li, Zhenqin and Fitzgerald, George and Kitson, David H. and Farnum, Martin and Fine, Richard M. and Kraut, Joseph and Hagler, Arnold T.}, year={1991}, month=dec, pages={263–270} }

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