PMID: 7018571May 26, 1981Paper

Methotrexate and folate binding to dihydrofolate reductase. Separate characterization of the pteridine and p-aminobenzoyl binding sites by resonance Raman spectroscopy

Biochemistry
Y OzakiP R Carey

Abstract

By using 324- and 350.6-nm excitation, it is possible to obtain selectively the resonance Raman spectra of the p-aminobenzoyl and pteridine chromophores, respectively, within methotrexate (MTX) or folate. Thus, for a single ligand, by changing the wavelength for excitation, the geometric conformations of both chromophores can be monitored separately. Resonance Raman spectra are reported for MTX bound to dihydrofolate reductases from Escherichia coli and from Lactobacillus casei, in each case in the presence and absence of NADPH. Additionally, some data are presented for enzyme-bound folate. The resonance Raman data support the conclusions of other workers that MTX binds with its pteridine ring protonated while the pteridine ring within folate is bound as a neutral species. However, for MTX, marked differences exist between the electronic distribution in the protonated pteridine ring for the ligand free in solution and for the bound species. The rearrangement of the pteridine electrons over and above that accompanying protonation explains the absorption properties of bound MTX, and together with protonation may account in part for the high affinity of MTX for the enzyme. The resonance Raman spectra show that slight differences e...Continue Reading

References

Aug 1, 1978·Quarterly Reviews of Biophysics·P R Carey
Oct 12, 1977·Journal of the American Chemical Society·S Scheiner, C W Kern

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Citations

Oct 3, 2002·Journal of the American Chemical Society·Yen-lin LinCarmay Lim
Aug 9, 2002·Journal of the American Chemical Society·Patrick AmstutzAndreas Plückthun

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