ISSN:0001-5792    

DOI:10.1159/000205844

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000205845

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000205846

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000205847

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000205848

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000205849

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

This paper summarizes various anomalies involving the duplicated y-globin genes which are normally arranged as -Gγ-Aγ-. Variations includeGγ→Aγand Aγ→Gγ replacements; newborn heterozygotes for these anomalies have low Gγ (AγAγ/¤γAγ) or high Gγ values (GγGγ/GγAγ). Additional abnormalities include the deletion of one γ-globin gene (-Aγ-; γ-thalassemia), γ-globin gene triplications (Gγ-AGγ-Aγ-; Gγ-Gγ-Aγ) and γ-globin gene quadruplications (Gγ-Gγ-Gγ-Aγ-); several of these conditions are found in different populations but at low frequencies. In adults, the Gγto Aγ ratio in the Hb F and often also the Hb F level, are directly related to specific structural characteristics of the chromosome; specific mutations in the promoter sequences 5’ to Gγor to Aγ, for instance, may result in increased Gγ or Aγ chain production with an increase in Hb F levels (nondeletional Gγ- or Aγ-HPFH) or with only modest changes in the total Hb F (normal adults; Swiss-HPFH). Simila

ISSN:0001-5792    

DOI:10.1159/000205850

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Human β-globin was produced in Escherichia coli as a cleavable fusion protein using the expression vector pLcII [Nagai and Thøgersen, Nature 301 p. 810, 1984]. The fusion protein CIIFXβ-globin was purified under denaturing conditions to homogeneity and the authentic β-globin was liberated by blood coagulation factor Xa. β-Globin was then folded and reconstituted with haem and α-subunits to form fully functional α2β2-tetramers [Nagai et al., Proc. natn. Acad. Sci. USA 82 p. 7252, 1985]. This has enabled us to produce mutants with amino acid substitutions in the β-subunit at will and in sufficient quantities to study their oxygen-binding properties and three-dimensional structures. We have crystallised three mutants, Hb Nympheas [Cys-930→Ser], Hb Daphne [Cys-93β→ Ser, His-143β → Arg] and Hb Sandra [Cys-93β→ Ser, Asp-940→ Glu], and have solved their structures to high resolution by

ISSN:0001-5792    

DOI:10.1159/000205851

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

It has been proposed that the process of ligand binding to hemoproteins is governed by sequential potential barriers as depicted in the following scheme [Austin et al., Biochemistry 14, pp. 5355–5373, 1975; An-sari et al., Proc. natn. Acad. Sci. USA, pp. 5000–5004, 1985]:Protein + ligand Protein-li

ISSN:0001-5792    

DOI:10.1159/000205852

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Reduction of five hemoglobins M (Hbs M) was studied using three enzymatic reducing systems; namely NADPH-flavin reductase from human erythrocytes, NADH-cytochrome b5 reductase from human erythrocytes and ferredoxin-NADP reductase from spinach. Under anaerobic conditions, abnormal chains in Hb M Saskatoon were reduced by all three systems, whereas those in Hb M Milwaukee were reduced by the latter two enzyme systems only. The abnormal chains in Hb M Hyde Park were reduced only by the ferredoxin-NADP reductase system. On the other hand, the abnormal chains in Hb M Iwate and Hb M Boston were reduced by sodium dithionite, but not by the three enzymatic reducing systems. Absorption and circular dichroic (CD) spectra of these Hbs M were compared with those of Hb A to examine their structural abnormalities. Absorption and CD spectra of four Hbs M except Hb M Milwaukee were remarkably different from those of Hb A. Conformational differences between α- and β-abnormal Hbs M were reflected in the CD spectrum of the ultraviolet region. The difference between the proximal and distal histidine-replaced Hbs M was also observed in the CD spectra of the visible regi

ISSN:0001-5792    

DOI:10.1159/000205853

出版商:S. Karger AG    

年代:1987

数据来源: Karger