Relationship between impaired glycation and the N-terminal structure of the Hb Görwihl [beta5(A2)Pro-->Ala] variant.
We studied the structural environment surrounding the beta-N-terminal glycation site of a hemoglobin (Hb) molecule in which the proline residue at beta5(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 [beta5(A2)Pro-->Ala]. On the basis of the results, we predicted that the glycation site would have the following characteristics: 1) glycation of the beta-N-terminus of Hb is probably accelerated by the neighboring histidine residue at beta2(NA2), which acts as an acid-base catalyst via a phosphate-mediated proton transfer; and 2) the mutation beta5(A2)Pro-->Ala would bring about impaired glycation of the N-terminal residue by forming an electrostatic bond between the alpha amino group of beta1(NA1)Val and beta carboxyl group of beta79(EF3)Asp.
Ito
Shigenori
S
Department of Physiological Chemistry, Osaka Medical College, Osaka, Japan. ito@art.osaka-med.ac.jp
Nakahari
Takashi
T
Yamamoto
Daisuke
D
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry; D003198:Computer Simulation; D006442:Glycated Hemoglobin / Q000737:chemistry*; D006031:Glycosylation; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011522:Protons; D055672:Static Electricity
D000596:Amino Acids; D006442:Glycated Hemoglobin; D006455:Hemoglobins, Abnormal; D011522:Protons; C470779:hemoglobin Görwihl