Amadori rearrangement potential of hemoglobin at its glycation sites is dependent on the three-dimensional structure of protein.

The site selectivity of nonenzymic glycation of proteins has been suggested to be a consequence of the Amadori rearrangement activity of the protein at the respective glycation sites [Acharya, A. S., Roy, R. P., & Dorai, B. (1991) J. Protein Chem. 10, 345-358]. The catalytic activity that determines the potential of a site for nonenzymic glycation is the propensity of its microenvironment to isomerize the protein bound aldose (aldimine) to a protein bound ketose (ketoamine). The catalytic power of the microenvironment of the glycation sites could be endowed to them either by the amino acid sequence (nearest-neighbor linear effects) or by the higher order structure (tertiary/quarternary) of the protein (nearest-neighbor three-dimensional effect). In an attempt to resolve between these two structural concepts, the glycation potential of Val-1(alpha) and Lys-16(alpha), the residues of hemoglobin A exhibiting the least and the highest isomerization activity in the tetramer, respectively, has been compared in the segment alpha 1-30, isolated alpha-chain, and the tetramer. When alpha-chain is used as the substrate for the nonenzymic glycation, the influence of the quaternary structure of the tetramer will be absent. Similarly, the contribution of the tertiary and quaternary structure of the protein will be absent when alpha 1-30 is used as the substrate. The microenvironment of Lys-16(alpha) exhibited hardly any Amadori rearrangement activity in the segment alpha 1-30. The tertiary structure of the alpha-chain induces a considerable degree of catalytic activity to the microenvironment of Lys-16(alpha) to isomerize the aldimine adduct at this site.(ABSTRACT TRUNCATED AT 250 WORDS)