METAL-INDUCED CONFORMATIONAL HETEROGENEITY OF TRANSFERRINS - A SPECTROSCOPIC STUDY OF INDIUM(III) AND OTHER METAL(III)-SUBSTITUTED TRANSFERRINS

The conformation in solution of three different metal(III)-transferrin s, namely aluminum(III), gallium(III) and indium(III) transferrin, was investigated by absorption, CD, H-1 NMR and C-13 NMR spectroscopies. The formation of the respective metal-transferrin complexes and the ch aracteristic 2:1 metal-to-protein binding stoichiometry were unambiguo usly demonstrated, in all cases, through UV difference studies. The C- 13 NMR spectra of these metallotransferrins in the carbonyl region are very similar to one another pointing out that the arrangement of the synergistic anion in the binding site must be essentially the same. Ho wever, the CD spectra in the near UV (aromatic region) reveal the occu rrence of significant differences between indium transferrin, on one s ide, and the other two derivatives, on the other. Also, the H-1 NMR sp ectra exhibit a number of different features suggesting the occurrence of metal-induced conformational heterogeneity around the metal sites. Such metal-induced conformational heterogeneity probably affects the transferrin-receptor recognition process, resulting in a different met abolic fate of these metals in the organisms. (C) 1995 Academic Press, Inc.