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Titolo: Glycated human hemoglobin (HbA1c): functional characteristics and molecular modeling studies.
Data di pubblicazione: 1998
Abstract: A minor hemoglobin component of human red cell hemolysate, HbA(1c), is the result of the non-enzymatic reaction of glucose with the α-amino groups of the valine residues at the N-terminus of the β-chains of human hemoglobin. In this paper, the effect of protons, chloride and 2,3- diphosphoglycerate (DPG) on the functional properties of HbA(1c) has been investigated in some details. Moreover, the structural modifications induced on the native molecule by the sugar moieties, studied by computer modeling, do agree with the observed functional alterations. In particular, the functional results indicate that: (a) the low-affinity conformation (or T- state) of HbA(1c) is destabilized by the chemical modification per se; (b) the Bohr effect is reduced with respect to that of native HbA0; (c) the affinity of the T-state of HbA(1c) for 2,3-diphosphoglycerate is about 2.6 X lower than that of the corresponding conformational state of HbA0, while the R-state is less affected with, the affinity being 1.7 X lower. At the structural level, computer modeling studies show that the two sugar moieties are asymmetrically disposed within the 2,3-diphosphoglycerate binding site. In addition, molecular mechanics and dynamics calculations concerning the interaction with 2,3-diphosphoglycerate indicate that while in HbA0 the effector can assume two different stable orientations, in glycated Hb only one orientation is possible. All together, the results show that glycation of the Val 1 residues of both β-chains does not impair the binding of DPG but imposes a different mode of binding by changing the internal geometry of the complex and the surface distribution of the positive electrostatic potential within the binding pocket
Tipologia:1.1 Articolo in rivista

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