Hb Baden: structural and functional characterization.
Hb Baden (β18Val→Met) is a rare variant hemoglobin that has never been functionally or clinically characterized. We describe a Hb Baden heterozygote who exhibits normal growth and development, as well as age- and gender-appropriate hematological values. Surprisingly, in vitro analyses demonstrate that Hb Baden is relatively unstable and exhibits an abnormally high affinity for O₂. These properties are likely to affect the physiologies of individuals who inherit the β(Baden) mutation in trans to a determinant for either a functionally relevant hemoglobinopathy or a mild thalassemia. The data also provide insights into the function of the A-helix/AB-segment of β globin, supporting a structural model in which this poorly understood region serves as a scaffold that fixes the positions of other helices that directly impact β-globin function.
Abdulmalik
Osheiza
O
Department of Pediatrics (Hematology), University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
Safo
Martin K
MK
Seeholzer
Steven H
SH
Asakura
Toshio
T
Hasbrouck
Nicole C
NC
Russell
J Eric
JE
D000293:Adolescent; D006453:Hemoglobinopathies; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D055544:beta-Globins / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D055544:beta-Globins; C554017:hemoglobin Baden; D010100:Oxygen