Compensatory secondary structure alterations in protein glycation.
Glycation, a local covalent interaction, leads to alterations in secondary and tertiary structures of hemoglobin, the changes produced by fructose being more pronounced than those caused by glucose. The Stokes diameter of hemoglobin increases upon glycation from 7 to 14 nm and a concurrent inter-chain cross-linking and heme loss are also observed, particularly in the later stage of glycation. An initial increase of tryptophan (trp) fluorescence was observed in both glucation and fructation. In case of frucation however there was a decrease in tryptophan fluorescence that was accompanied by an increase in fluorescence of the advanced glycosylation end products (AGEs). This fluorescence behavior is indicative of energy transfer between tryptophan and the AGEs formed during the late stage of glycation. Emergence of an isosbestic point in the fluorescence spectra (taken at different time intervals) implies existence of two distinct glycation stages. The late glycation stage is also marked by an increase of beta structure and random coil at the expense of alpha helix. It is further observed that this compensatory loss of alpha helix (reported for the first time) and increase in beta sheet and random coil elements depend on the number of solvent-accessible glycation sites (rather than total number of such sites) and the subunit assembly of the protein.
GhoshMoulick
Ranjita
R
Department of Biochemistry, Calcutta University, 35 Ballygunge Circular Road, Calcutta 700019, India.
Bhattacharya
Jaydeep
J
Roy
Shibsekhar
S
Basak
Soumen
S
Dasgupta
Anjan Kr
AK
D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D005453:Fluorescence; D005947:Glucose / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
D017127:Glycation End Products, Advanced; D011506:Proteins; D006418:Heme; D005947:Glucose