Hemoglobin Einstein: semisynthetic deletion in the B-helix of the alpha-chain.
The influence of the deletion of the tetra peptide segment alpha(23-26) of the B-helix of the alpha-chain of hemoglobin-A on its assembly, structure, and functional properties has been investigated. The hemoglobin with the deletion, ss-Hemoglobin-Einstein, is readily assembled from semisynthetic alpha(1-141) des(23-26) globin and human betaA-chain. The deletion of alpha(23-26) modulates the O2 affinity of hemoglobin in a buffer/allosteric effector specific fashion, but has little influence on the Bohr effect. The deletion has no influence on the thermodynamic stability of the alpha1beta1 and the alpha1beta2 interface. The semisynthetic hemoglobin exhibits normal intersubunit interactions at the alpha1beta1 and alpha1beta2 interfaces as reflected by 1H-NMR spectroscopy. Molecular modeling studies of ss-Hemoglobin-Einstein suggest that the segment alpha(28-35) is in a helical conformation, while the segment alpha(19-22) is the nonhelical AB region. The shortened B-helix conserves the interactions of alpha1beta1 interface. The results demonstrate a high degree of plasticity in the hemoglobin structure that accommodates the deletion of alpha(23-26) without perturbing its overall global conformation.
Srinivasulu
Sonati
S
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Manjula
Belur N
BN
Nagel
Ronald L
RL
Tsai
Ching-Hsuan
CH
Ho
Chien
C
Prabhakaran
Muthuchidambaran
M
Acharya
Seetharama A
SA
D006441:Hemoglobin A / Q000737:chemistry* / Q000302:isolation & purification; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D017384:Sequence Deletion; D013816:Thermodynamics
D006455:Hemoglobins, Abnormal; D010455:Peptides; D021122:Protein Subunits; C493514:hemoglobin Einstein; D006441:Hemoglobin A; D010100:Oxygen