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The Structure of Hb S

In SCD the normal adult Hb A is replaced by the mutant sickle Hb S (a2bS2 ). For the Hb S mutant, the single amino acid substitution, b6 Glu Val, leads to intermolecular Hb S interactions when Hb S is in the deoxygenated state. It is important to note that conformational changes take place upon O2 loading/unloading, such that the oxygenated ("relaxed"; R) and deoxygenated ("tense"; T) states of the Hb molecule are distinct[47]. The structure and identity of amino acid side chains at certain sites in the 8 a -helixes (designated A-H) of each globin subunit of Hb is fundamental to these O2-dependent interactions. In the Hb S mutant, the b6 Val of one bS-globin chain  in the A-helical fold undergoes a hydrophobic interaction with a hydrophobic "pocket" region in E-F region of  another bS-globin chain when Hb S is in the deoxygenated state[52]. A donor-acceptor interaction takes place between two adjacent Hb S molecules such that the b6 Val, or bS-"donor" site interacts with the hydrophobic b85 Leu and b88 Phe residues of the E-F region, which together form a bS-"acceptor" region[52].