Hb Villaverde [beta 89 (F5) Ser-->Thr]: the structural modification of an intrasubunit contact is responsible for a high oxygen affinity.
Hb Villaverde [beta 89 (F5) Ser-->Thr], identified in a Spanish patient, is a new human hemoglobin variant, electrophoreticaly silent, responsible for a severe erythrocytosis. This abnormal hemoglobin displays a very high oxygen affinity and a markedly reduced cooperativity that is partly restored in the presence of IHP. Determination of the structural abnormality was achieved on a mixture of the normal and abnormal beta-chains. After isolation of the abnormal tryptic peptide by RP-HPLC, its sequence was determined by mass spectrometry. The structural abnormality disturbs the intrasubunit interaction between helices F and H and, thus, may weaken the C-terminal bonds of the deoxy conformation and the heme contacts of several hydrophobic residues. Hb Villaverde demonstrates that this intrasubunit contact between helices F and H is essential for the cohesion of the hemoglobin molecule.
Wajcman
H
H
INSERM U299, Hôpital de Bicêtre, Le Kremlin, France.
Kister
J
J
Promé
D
D
Galacteros
F
F
Gilsanz
F
F
D000328:Adult; D000595:Amino Acid Sequence; D001772:Blood Cell Count; D002675:Child, Preschool; D006400:Hematocrit; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010100:Oxygen / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D011086:Polycythemia / Q000097:blood* / Q000235:genetics; D012694:Serine; D013912:Threonine; D014357:Trypsin
D006455:Hemoglobins, Abnormal; D010446:Peptide Fragments; D013912:Threonine; D012694:Serine; D014357:Trypsin; D010100:Oxygen