X-ray crystal structure of acetyl-iMet–β^S-globin with iMet–α-globin modified HbS (CRYST 1) showing altered α-cleft and β-cleft. The CO-ligated structure of the modified HbS is in the R2 state previously described for structures of aldehyde modified HbS.^4,32  (A) Structure of acetyl-iMet–β^S-globin with iMet-α–globin modified HbS shows that the 2 iMet residues (cyan spheres) at the α-globin chains nearly fill the α-cleft. (B) Close interactions of iMet (contoured with final 2F_o-F_c electron density at 0.8σ) with residues from α1- and α2-globin chains. (C) The α-cleft region in the structure of acetyl-iMet–β^S-globin with iMet–α-globin (cyan) is compared with the same region of a structure of HbS modified by the covalently bound antisickling aromatic aldehyde TD-7 (magenta). (D) The β-cleft of acetyl-iMet–β^S-globin with iMet–α-globin is shown with the acetyl-iMet residues highlighted (magenta). (E) Close interactions of acetyl-iMet (contoured with final 2F_o-F_c electron density at 0.6σ) with residues from the β1- and β2-globin chains.