Chloride masks effects of opposing positive charges in Hb A and Hb Hinsdale (beta 139 Asn-->Lys) that can modulate cooperativity as well as oxygen affinity.

In the human hemoglobin variant Hb Hinsdale, lysine is substituted for asparagine at position beta 139 (H17), which lies in the water-filled cavity that runs through the center of the molecule. This substitution adds two extra cationic residues to the excess of four cationic residues normally lining this cavity. Moo-Penn and colleagues who discovered this hemoglobin, found its oxygen affinity in 0.

Accommodation of insertions in helices: the mutation in hemoglobin Catonsville (Pro 37 alpha-Glu-Thr 38 alpha) generates a 3(10)-->alpha bulge.

Hemoglobin Catonsville is a mutation of human hemoglobin (an alpha 2 beta 2 tetramer) in which a glutamate residue is inserted into the first turn of a highly conserved 3(10) helix (the C helix) of each alpha subunit. In theory, amino acid insertions (or deletions) in protein helices can be accommodated via two distinct mechanisms. One, termed the register shift mechanism, preserves the geometry of the helix while requiring all of the residues on one flank of the insertion site to rotate by 100 degrees in the case of an alpha helix or by 120 degrees in the case of a 3(10) helix.

Mutagenic dissection of hemoglobin cooperativity: effects of amino acid alteration on subunit assembly of oxy and deoxy tetramers.

Free energies of oxygen-linked subunit assembly and cooperative interaction have been determined for 34 molecular species of human hemoglobin, which differ by amino acid alterations as a result of mutation or chemical modification at specific sites. These studies required the development of extensions to our earlier methodology. In combination with previous results they comprise a data base of 60 hemoglobin species, characterized under the same conditions.

Hb Rancho Mirage [beta 143(H21)His----Asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH.

Hb Rancho Mirage was detected in a 17-year-old male in association with a mild anemia. Hemoglobin electrophoresis revealed the variant had a mobility between Hbs A and J on cellulose acetate (pH 8.6) and a mobility like Hb F on citrate agar (pH 6.

[Hemoglobin Setif (alpha 94 (G1) Asp----Tyr) in a Spanish family].

A family was studied who carried a slow mobility haemoglobin on cellulose acetate electrophoresis at pH 8.6. The structural analysis of the anomalous globin chain showed substitution of residual aspartic acid in position 94 of the alpha chain by tyrosine (Hb Setif).

Purification and characterization of a pilin specific for Brazilian purpuric fever-associated Haemophilus influenzae biogroup aegyptius (H. aegyptius) strains.

Brazilian purpuric fever (BPF) is a recently described fatal pediatric disease caused by systemic infection with Haemophilus influenzae biogroup aegyptius. Previous studies have shown that all H. influenzae biogroup aegyptius strains isolated from BPF cases and case contacts share several unique phenotypic and genotypic characteristics that differentiate them from other H.

Structural, functional, and subunit assembly properties of hemoglobin Attleboro [alpha 138 (H21) Ser----Pro], a variant possessing a site maturation at a critical C-terminal residue.

Hemoglobin Attleboro, a new alpha-chain variant with a substitution of proline for serine at position 138 (H21), was found to be a noncooperative high-affinity hemoglobin (P50 = 0.26 mmHg at pH 7 and 20 degrees C) which lacked an alkaline Bohr effect. Addition of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate (IHP) led to a decrease in oxygen affinity but to no alteration in either Bohr effect or cooperativity.

Hb Catonsville (glutamic acid inserted between Pro-37(C2)alpha and Thr-38(C3)alpha). Nonallelic gene conversion in the globin system?

Hb Catonsville is an unstable variant in which glutamic acid is inserted into the alpha-globin chain between Pro-37(C2) and Thr-38(C3). The peptide sequence data are consistent with the DNA sequence of the polymerase chain reaction-amplified fragment of the variant globin gene, which shows the insertion of the triplet codon--GAA--into the mutant alpha-globin gene. In the normal alpha-globin gene cluster the codon for glutamic acid is GAG rather than GAA.

Hb Hinsdale [beta 139 (H17)Asn----Lys]: a variant in the central cavity showing reduced affinity for oxygen and 2,3-diphosphoglycerate.

Hb Hinsdale was detected in two sisters and in a son and daughter of one of them as a band migrating in the Hb F position on cellulose acetate, pH 8.5. On citrate agar (pH 6.

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

Hemoglobin Brockton [beta 138 (H16) Ala----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 properties of the variant are very similar to those of Hb A.

A case of hemoglobin Indianapolis [beta 112(G14) Cys----Arg] in an individual from Cordoba, Spain.

Hemoglobin Indianapolis was first described by Adams et al (1,2) as a very unstable variant with a phenotype similar to severe beta-thalassemia. We have also characterized this variant, but there are several differences in the clinical expression of the variant described in our report and those described in the original case. We found Hb Indianapolis to be unstable, but not to the extent that it could not be detected by routine testing.

Hemoglobin New Mexico: beta 100 (G2) Pro----Arg. A variant hemoglobin associated with erythrocytosis.

Hemoglobin New Mexico beta 100 Pro----Arg was found in a 4-year-old black male and represents a new mutation. The propositus is also heterozygous for Hb S. The variant shows high oxygen affinity, reduced cooperatively, and a lowered alkaline Bohr effect.

Separation of hemoglobin variants by ion-exchange chromatography on Monobead resins.

Our studies on the separation of hemoglobin variants using Monobead ion exchangers show that these ion exchangers will resolve variants that heretofore could not be resolved. Procedures with these ion exchangers, therefore, extend our ability to detect hemoglobinopathies. Since it is also important to study the physicochemical properties of variants, their isolation is of critical importance to the researcher.

Structural and functional studies of hemoglobin Wayne: an elongated alpha-chain variant.

Hemoglobin Wayne (Hb Wayne) is a frame-shift, elongated alpha-chain variant that exists in two forms, with either asparagine or aspartic acid as residue 139. Oxygen equilibrium studies showed that stripped Hb Wayne Asn and Hb Wayne Asp possessed high oxygen affinity (P 1/2 = 0.60 and 0.

Hemoglobin Shelby [beta 131(H9) Gln----Lys] a correction to the structure of hemoglobin Deaconess and hemoglobin Leslie.

Hemoglobin Shelby, detected in two unrelated black families, has an electrophoretic mobility like Hb F on cellulose acetate (pH 8.4) and a mobility between Hbs S and C on citrate agar (pH 6.2).

The effect of bloodletting on exercise performance in a subject with a high-affinity hemoglobin variant.

We studied two young army recruits with erythrocytosis. One had a variant hemoglobin with high affinity for oxygen (hemoglobin Osler, also known as Fort Gordon and Nancy, beta 145 Tyr leads to Asp). The other had normal oxygen affinity and erythrocytosis of undetermined etiology.

Hemoglobin Evanston: alpha 14(A12) Trp leads to Arg. A variant hemoglobin associated with alpha-thalassemia-2.

Hb Evanston (alpha 14 Trp leads to Arg) was detected on cellulose acetate at pH 8.4 as a band with an electrophoretic mobility similar to that of Hb S. In addition, a band migrating cathodic to Hb A2 suggested the presence of a variant Hb A2 with a substitution in the alpha-chain, a fact that was later confirmed by structural analysis.