Structural analysis of the elongated part of an abnormal hemoglobin "Hemoglobin Cranston"

Haemoglobin variants in which a frameshift results in chain elongation are unusual. Haemoglobin Cranston (HbCranston) is an unstable haemologin firstly with abnormal elongation. Concerning the pathogenesis of HbCranston, the insertion of the repeated pair nucleotide pair AG into beta mRNA between the triplet codon of 144 Lysine (AAG) and 145 Tyrosine (UAU) is the main abnormality. It is assumed to be due to an insertion of the dinucleotide CA into codon 146 [CACCA( CA) C] which abolishes the normal stop codon at position 147 (Bunn et al, 1975). This abnormality causes a frameshift, which results in elongation of the b chain amino acids. Here, the author performs a bioinformatic analysis to study the secondary and tertiary structures of those elongated amino acid sequences. Answering this question, a computer-based study for protein structure modeling is performed. According to this study, the secondary structure analysis of the elongated part of Hb Cranston showed eleven additional helices to the normal b globin chains. Based on this information, the main alteration in the Hb Cranston might be due to the additional helices in the elongated part. Concerning the tertiary structure, the increase of folds, accompanied with the aberration in secondary structure of globin in Hb Cranston can be identified.