Hb Sitia [beta128(H6)Ala-->Val]: an unstable variant with a substitution in the alpha1beta1 interface.
Hb Sitia [beta128(H6)Ala-->Val] was found in a Greek female with slightly reduced red blood cell indices. The abnormal hemoglobin was indistinguishable from Hb A by electrophoresis but eluted after Hb A on cation exchange high performance liquid chromatography. DNA sequence analysis revealed a GCT-->GTT mutation at codon 128, which is predicted to encode an Ala-->Val substitution. This was confirmed by mass spectrometry analyses of the beta-globin chain. Since alanine at beta128(H6) interacts with several amino acids of the alpha1beta1 contact, its replacement by a larger residue results in a mild instability of the molecule and slight modifications of the oxygen binding properties.
Papassotiriou
I
I
Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece.
Traeger-Synodinos
J
J
Promé
D
D
Kister
J
J
Vrettou
C
C
Xaidara
A
A
Marden
M
M
Stamoulakatou
A
A
Wajcman
H
H
Kanavakis
E
E
D000328:Adult; D019943:Amino Acid Substitution; D002852:Chromatography, Ion Exchange; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005914:Globins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D006115:Greece; D006366:Heinz Bodies / Q000648:ultrastructure; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D020125:Mutation, Missense; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012333:RNA, Messenger / Q000097:blood; D011990:Receptors, Transferrin / Q000097:blood; D014158:Transcription, Genetic
D003062:Codon; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C434203:hemoglobin Sitia; D004921:Erythropoietin; D005914:Globins; D010100:Oxygen