Phosphorus-31 nuclear magnetic resonance studies of the binding of oxidized coenzymes to Lactobacillus casei dihydrofolate reductase

Biochemistry. 1980 Aug 5;19(16):3746-54. doi: 10.1021/bi00557a016.

Abstract

The 31P NMR spectra of NADP+ and a number of its structural analogues have been obtained from their binary and ternary complexes with Lactobacillus casei dihydrofolate reductase. The 2'-phosphate resonance is shifted downfield 2.7-2.9 ppm in all cases. Line-shape analysis of this resonance as a function of coenzyme concentration gave values for the dissociation rate constant of the coenzyme from many of the complexes. The values obtained are discussed in terms of the kinetic mechanism of coenzyme binding. The chemical shifts of the pyrophosphate resonances vary from one complex to another over a range of 3.8 ppm. The assignment of these signals to the individuals pyrophosphate 31P nuclei and the structural origins of the chemical shift changes are discussed. From these data, and the 1H NMR experiments describedin the preceding paper [Hyde, E. I., Birdsall, B., Roberts, G. C. K., Feeney, J., & Burgen, A. S. V. (1980) Biochemistry (third paper of four in this issue)], it is concluded that the "nicotinamide" end of the thionicotinamide and acetylpyridine coenzyme analogue binds to the enzyme quite differently from that of the natural coenzyme NADP+.

MeSH terms

  • Binding Sites
  • Kinetics
  • Lacticaseibacillus casei / enzymology*
  • Magnetic Resonance Spectroscopy
  • Mathematics
  • NADP* / analogs & derivatives
  • Oxidation-Reduction
  • Protein Binding
  • Tetrahydrofolate Dehydrogenase / metabolism*

Substances

  • NADP
  • Tetrahydrofolate Dehydrogenase