Hemoglobin sickle-cell

Lesk and Chothia did find, however, that there is a striking preferential conservation of the hydrophobic character of the amino acids at the 59 buried positions, but that no such conservation occurs at positions exposed on the surface of the molecule. With a few exceptions on the surface, hydrophobic residues have replaced hydrophilic ones and vice versa. However, the case of sickle-cell hemoglobin, which is described below, shows that a charge balance must be preserved to avoid hydrophobic patches on the surface. In summary, the evolutionary divergence of these nine globins has been constrained primarily by an almost absolute conservation of the hydro-phobicity of the residues buried in the helix-to-helix and helix-to-heme contacts. 

Sickle-cell hemoglobin confers resistance to malaria... 

Figure 3.14 Sickle-cell hemoglobin molecules polymerize due to the hydrophobic patch introduced by the mutation Glu 6 to Val in the P chain. The diagram (a) illustrates how this hydrophobic patch (green interacts with a hydrophobic pocket (red) in a second hemoglobin molecule, whose hydrophobic patch interacts with the pocket in a third molecule, and so on. Electron micrographs of sickle-cell hemoglobin fibers are shown in cross-section in (b) and along the fibers in (c). [(b) and (c) from J.T. Finch et al., Proc. Natl. Acad. Set. USA 70 718-722, 1973.)...

Finch, J.T., et al. Stmcture of sickled erythrocytes and of sickle-cell hemoglobin fibers. Proc. Natl. Acad. Sci. USA 70 718-722, 1973. 

In sickle cell hemoglobin (HbS), Val replaces the P6 Glu of HbA, creating a sticky patch that has a complement on deoxyHb (but not on oxyHb). De-oxyHbS polymerizes at low O2 concentrations, forming fibers that distort erythrocytes into sickle shapes. 

In sickle cell hemoglobin, the glutamic acid of the beta subunit is replaced by the amino acid valine (Fig. 7.11.2). Even though only this one amino acid is... 

Aromatic side chains of amino acids such as phenylalanine, tryptophan, and tyrosine are found in general in the interior of proteins, in hydrophobic regions. In some proteins they mediate helix-helix contacts. It is to be expected that agents containing aromatic groups could interact with proteins via aromatic-aromatic interactions, as for instance, proven by X-ray studies of biphenyl compounds which inhibit sickle-cell hemoglobin gelation. 

Sickle cell trait Sickle cell anemia Sickle cell hemoglobin C... 

Compare this situation with that for normal and sickle cell hemoglobins. The two COX enzymes are both fully functional and differ by a single conservative amino acid replacement. In contrast, normal hemoglobin is fully functional but sickle cell hemoglobin is not and these differ by a single nonconservative amino acid replacement (see chapter 11). 

Deoxygenated sickle cell hemoglobin (deoxyHbS), the j8-Glu-6-Val point mutant form of adult hemoglobin, appears to obey the following empirical rate law for nucleation of polymerization ... 

Basis of the Sickle-Cell Mutation Sickle-cell hemoglobin has a Val residue at position 6 of the j3-globin chain, instead of the Glu residue found in normal hemoglobin A. Can you predict what change took place in the DNA codon for glutamate to account for replacement of the Glu residue by Val ... 

Ingram showed that normal and sickle-cell hemoglobin differ in a single amino acid residue. 

AE0 change in redox potential under HbS sickle cell hemoglobin... 

Know the molecular etiology for the various types of abnormal hemoglobins and their 02-binding peculiarities, including sickle cell hemoglobins. 

Josephs R Research on sickle cell hemoglobin, virtual tour of sickle hemoglobin polymerization. Laboratory for Electron Microscopy at the University of Chicago, 1999. Available at http // gingi. uchicago. eduZsc2-tourl.htm, 2004. 

There are many abnormal or mutant hemoglobins, some of which cause pathological conditions. One is sickle-cell hemoglobin (HbS), in which the glutamate residue in the sixth position of the normal human hemoglobin (HbA) /3 chain has been replaced by valine. This position, referred to as /36, is on the outside of the hemoglobin molecule. Individuals who... 

Sickle cell hemoglobin C Painless hematuria and rare aseptic necrosis of bone vasoocclusive crises are less common and occur later in life other complications are ocular disease and pregnancy-related problems mild anemia (Hb 10-12 g/dL)... 

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