The amino acid compositions of enterotoxin C strain 137 and enterotoxin C strain 361 were determined with a Spinco amino acid analyzer. Glutamic acid was determined as the N-terminal amino acid

Hemoglobin Cowtown [His HC3(146)-beta----Leu] exhibits high oxygen affinity and a halved alkaline Bohr effect. X-ray analysis shows the COOH-terminal leucine to be in equilibrium between two positions: one with the salt bridge between the terminal carboxyl and Lys C5(40)alpha intact and the leucyl side chain leaning against main chain atoms of helices F and FG and the other with the terminal salt bridge broken and the leucyl side chain touching Pro C2(37)alpha. Structural changes are confined to the immediate neighborhood of the COOH terminus, showing the halving of the alkaline Bohr effect to be due directly to the loss of the histidine, without significant contributions from changes in pK values of other ionizable groups due to structural changes elsewhere.

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To date 88 abnormal hemoglobins have been described with altered oxygen affinities. Of these, 60 variants have high affinity and 28 have low affinity. Twenty-six of these abnormal hemoglobins are chemically unstable. Twenty-seven of the high affinity hemoglobins are associated with erythrocytosis. An equal number are not associated with increased red cell mass. Anemia has been reported with 13 of the low affinity variants; however, the primary cause of the anemia of many may be the concurrent chemical instability. A strong correlaton can be shown for stable variants with altered oxygen affinity between the P50 value of the red cell and the hemoglobin concentration of the affected individual's blood. Hemoglobin variants with altered oxygen affinity can be classified into groups depending upon the amino acid change in specific structural sites. The sites include subunit interfaces, heme contacts, central cavity, DPG binding site, C-terminus, and other external and internal residues. Functional studies of six abnormal hemoglobins, four at the beta 101 residue in the central cavity near the alpha 1 beta 2 interfce, one near the DPG binding site and one at the C-terminus of the beta chain, indicate that the exact explanation of the structure-function relationship in hemoglobin depends upon the specific residue that is altered and the chemical properties of the substituted group. Comparative studies of multiple variants of the same position should provide insight into the role of critical residues in the binding of oxygen by hemoglobin.

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