Hemoglobin Providence Asn and Hemoglobin Providence Asp are two abnormal hemoglobins which apparently arise from a single genetic change that substitutes asparagine for lysine at position 82 (EF6) in the j3 chain of human hemoglobin. The second form appears to be the result of a partial in uiuo deamidation of the asparagine situated at position /382. Cellulose acetate and citrate agar electrophoresis of hemolysates from patients with this abnormality shows three bands. Globin chain electrophoresis at acid and alkaline pH shows three /3 chains. These three chains correspond to the normal PA chain and two abnormal fi chains. Sequence analysis indicates that the two abnormal chains differ from PA at only position /382. In the two abnormal chains, the residue which is normally lysine is substituted either by asparagine or by aspartic acid. These substitutions are notable because j382 lysine is one of the residues involved in 2,3-diphosphoglycerate binding. Additionally, p82 lysine is typically invariant in hemoglobin /3 chain sequences. Sequence data on the two forms of Hemoglobin Providence are given in this paper. The functional properties of these two forms are described in the next paper.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAccommodation of insertions in helixes: The mutation in hemoglobin catonsville (Pro 37.alpha.-Glu-Thr 38.alpha.) generates a 310 .fwdarw. .alpha. bulgeJeffrey S. Kavanaugh, Winston F. Moo-Penn, and Arthur ArnoneCite this: Biochemistry 1993, 32, 10, 2509–2513Publication Date (Print):March 16, 1993Publication History Published online1 May 2002Published inissue 16 March 1993https://pubs.acs.org/doi/10.1021/bi00061a007https://doi.org/10.1021/bi00061a007research-articleACS PublicationsRequest reuse permissionsArticle Views186Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Hemoglobin Catonsville is a mutation of human hemoglobin (an alpha2beta2 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. The other, termed the bulge (or indentation) mechanism, distorts the local geometry of the helix but does not alter the helix register. High-resolution X-ray diffraction analysis of deoxyhemoglobin Catonsville shows that the inserted residue is accommodated as a bulge, demonstrating that this is a viable mechanism. (In contrast, no such evidence is yet available for the register shift mechanism.) More specifically, the insertion converts one turn of the C helix from 3(10) geometry to alpha helix-like geometry, raising the possibility that a common mechanism for accommodating insertions and deletions within helices may involve localized interconversions between 3(10), alpha, and pi helical structures.

(1993). Characterization of HB Volga [B27(B9)ALA→ASP] and HB J-Wenchangwuming [α11(A9)LYS→GLN] in the Population of the United States. Hemoglobin: Vol. 17, No. 1, pp. 67-71.

(1991). HB Luxembourg [α24(B5)TYR→HIS], HB Maputo [β47(CD6)ASP→TYR], and HB Fukuyama [β77(EF1)HIS→TYR] Hemoglobin: Vol. 15, No. 1-2, pp. 97-101.

The evaluation of a family with chronic mild anemia led to the identification of a new unstable hemoglobin (Hemoglobin Cheverly). Modest anemia and reticulocytosis, normal to slightly increased mean corpuscular volume (MCV), and normal mean corpuscular hemoglobin concentration (MCHC) were present in the affected family members. Electrophoresis of blood samples on cellulose acetate and on citrate agar revealed normal patterns. Globin chain analysis and isoelectric focusing data were also normal. After incubation for 3 h at 41 degrees C, Heinz bodies were detected in 95-100% of erythrocytes from affected individuals. Positive heat and isopropanol tests confirmed the initial observation of the Heinz body preparation and indicated that an unstable hemoglobin was present. Structural analysis showed an amino acid substitution of Phe-Ser at position 45 (CD4) in the beta chain. Hemoglobin Cheverly has a reduced affinity for oxygen and a reduced Bohr effect, properties that can be rationalized on the basis of the x-ray crystallographic structure of normal hemoglobin. Despite structural and functional similarities between Hb Cheverly and Hb Hammersmith, beta 42 (CD1) Phe-Ser, the clinical manifestations of Hb Cheverly are mild in contrast to the severe disease observed with Hb Hammersmith. Reasons for the apparently silent clinical expression of Hb Cheverly are not known. We discuss the implications of unstable hemoglobins in the evaluation of chronic anemia in pediatric patients.

Hemoglobin J Rovigo was first described by Alberti et al. (1) in an Italian family. Our report concerns the identification and fuctional properties of this variant in combination with β-thalassemia in a Brazilian family.

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the β chain: β6 Glu → Val and β142 Ala→ Val. The β6 Glu→Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3‐bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

A hemoglobin mutant with the mobility of hemoglobin (Hb) A on alkaline cellulose acetate or starch gel electrophoresis and mobility between Hb A and Hb S on citrate agar electrophoresis was detected in a patient with erythrocytosis. Structural analysis shows a substitution of histidine by tyrosine at position 145 in the β-chain.