Relationship Between Impaired Glycation and the N-Terminal Structure of the Hb Görwihl [β5(A2)Pro→Ala] Variant

Abstract

We studied the structural environment surrounding the β-N-terminal glycation site of a hemoglobin (Hb) molecule in which the proline residue at β5(A2) was substituted by alanine in silico. By computer analysis that used Protein Data Bank data (PDB ID: 1BZ0), we tried to clarify the reason for impaired glycation of Hb Görwihl [β5(A2)Pro→Ala]. On the basis of the results, we predicted that the glycation site would have the following characteristics: 1) glycation of the β-N-terminus of Hb is probably accelerated by the neighboring histidine residue at β2(NA2), which acts as an acid-base catalyst via a phosphate-mediated proton transfer; and 2) the mutation β5(A2)Pro→Ala would bring about impaired glycation of the N-terminal residue by forming an electrostatic bond between the α amino group of β1(NA1)Val and β carboxyl group of β79(EF3)Asp.

Keywords:

• Hb A_1c
• Hemoglobin (Hb)
• Variant
• Glycation
• Phosphate
• Site specificity