Characterization of hemoglobin Würzburg (alpha2beta2 4(A1)Thr-->Asn), a new electrophoretically silent variant, by mass spectrometry and molecular modeling studies.
The first hemoglobin (Hb) variant carrying a mutation at beta4 was identified as beta4(A1)Thr-->Asn or Hb Würzburg and constituted 38% of the total hemoglobin. It showed a slightly elevated oxygen affinity and a slightly decreased cooperativity index (n50 = 2.3 versus n50 = 2.8). The analysis of the electrostatic potential showed an increased negative charge at the site of the mutation with a displacement of beta6(A3)Glu by 1.3A. The replacement of threonine by asparagine seems to stabilize the R conformation. This may explain partially both the high affinity and the reduction in cooperativity.
Bissé
Emmanuel
E
Department of Clinical Chemistry, University Hospital, Hugstetterstrasse 55, D-79106 Freiburg, Germany. bisse@med1.ukl.uni-freiburg.de
Zorn
Nathalie
N
Boussert
Stéphanie
S
Epting
Thomas
T
Van Dorsselaer
Alain
A
Horst
Jürgen
J
Baumstark
Manfred
M
Wieland
Heinrich
H
D019943:Amino Acid Substitution; D004247:DNA / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006455:Hemoglobins, Abnormal; C511809:hemoglobin Würzburg; D004247:DNA