Hemoglobin Brockton [.beta.138 (H16) Ala .fwdarw. Pro]: an unstable variant near the C-terminus of the .beta.-subunits with normal oxygen-binding properties

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Abstract
Hemoglobin Brockton [.beta.138 (H16) Ala .fwdarw. Pro] is an unstable variant associated with a mild anemia. It has the same electrophoretic mobility as and cannot be resolved from Hb A. Oxygen affinity measurements of blood and hemolysate do not indicate biphasic oxygen saturation, showing that the functional perperties of the variant are very similar to those of Hb A. This implies that the introduction of proline into the H-helix at position 138 does not disrupt the critical inter- and intrasubunit hydrogen bonds and salt bridges at the .beta. carboxyl-terminal dipeptide, since these polar interactions are essential for the normal oxygen-binding properties of hemoglobin. X-ray crystallographic data are consistent with these findings and show that the consequences of the .beta.138 Ala .fwdarw. Pro substitution are almost entirely confined to the immediate vicinity of the mutation site. Instability probably results from the inability of a buried hydrogen bond to form between Pro 138.beta. and Val 134.beta.