A chain of human hemoglobin

In order to find an explanation for the observed hydrolysis of bonds which are usually difficult to split, it is helpful to examine the nature of the amino acid sequence around the unusual bonds and consider the conditions employed for hydrolysis when these bonds were split. From the data in Table VI it appears that after hydrolysis of bonds formed by the aromatic amino acids and leucine, bonds of methionine, glutamine, asparagine, histidine, lysine, and threonine are most susceptible to chymotrypsin. Certainly, many of these bonds are split slowly, and within the same substrates several bonds formed by the carboxyl groups of the same amino acids were not hydrolyzed to a detectable extent. Thus, in the a-chain of human hemoglobin only one of the four asparaginyl bonds, three of the eight histidyl bonds, and one of the eleven lysyl bonds were hydrolyzed. Similar results are obtained with the other substrates. 

Chymotrypsin does not hydrolyze extensively bonds formed by the imino group of proline. Bonds of this type were not cleaved in ribo-nuclease, c3rtochrome c, and the a-chain of human hemoglobin. The -Phe-Pro- bond in ovine corticotropin has been reported to be hydrolyzed by chymotrypsin. The extent of hydrolysis was low as judged by the 6 % yield of the peptide which contained the carboxyl-terminal phenylalanine of the -Phe-Pro- bond. 

DNA diagnostics. Representations of sequencing gels for variants of the a chain of human hemoglobin are shown here. What is the nature of the amino acid change in each of the variants The first triplet encodes valine. 

Fig. 1. Two-dimensional presentation of the spatial arrangement of the amino acid residues of the a chain of human hemoglobin. 9 Residues in contact with the heme group, % Residues that participate in the aijSi contact. Residues that participate in the ai a contact.

Secondary structure of the a chain of human hemoglobin. The helical regions (labeled A-H, after Kendrew), N and C termini, and the histidines located near the heme group are indicated. The axes of the B and C helices are indicated by dashed lines. Note that the a chain lacks helix D present in the /S chain. The amino acid residues are numbered by two different methods from the N terminus of the polypeptide chain and from the N-terminal amino acid residue of each helix. Nonhelical regions are designated by the letters of helices at each end of a region. 

ESI-MS spectrum of the a-chain of human hemoglobin. Reprinted with permission from the Journal of Chemical Education, 1996, Vol. 73, No. 4, pp. A82-A88 copyright 1996, Division of Chemical Education, Inc. 

Figure 7-23 Folding pattern of the hemoglobin monomers. The pattern shown is for the P chain of human hemoglobin. Some of the differences between this and the a chain and myoglobin are indicated. Evolutionarily conserved residues are indicated by boxes, I I highly conserved, I I invariant. Other markings show substitutions observed in some abnormal human hemoglobins. Conserved residues are numbered according to their location in one of the helices A-H, while mutant hemoglobins are indicated by the position of the substitution in the entire a and P chain.

Repetitions of di-, tri-, and tetrapeptides in random sequences corresponding to ribonuclease (R), TMV protein, chymotrypsinogen (C), trypsinogen (T), a and /3 chains of human hemoglobin. Means (x) and standard deviations (sd) for 60 sequences of each type. Figures in parentheses are the values for the naturally occurring sequences. 

Hydrolysis in dilute acid under conditions which lead to the preferential rupture of aspartyl bonds may provide an excellent means for specific cleavage of polypeptides and proteins. Of all acid degradative techniques, hydrolysis in dilute acid appears to be the most specific and closely approaches the specificity of certain proteolytic enzymes. This method, however, has not been applied widely to problems on sequence analysis. Ingram and Stretton (1962) hydrolyzed a tridecapeptide from the S-chain of human hemoglobin A2 for 12 hr at 105°C in 0.25 M acetic acid. Prefer-... 

Fig. 5. The hydrolysis of several peptides from a- and jS-chains of human hemoglobin by papain. Hydrolyses were performed at for 15-18 hr at pH 5.5,...

Secondary structure of the p chain of human hemoglobin. The helical regions (labeled A-H, after Kendrew), N and C termini, and the histidines located near the heme group are indicated. The axes of the B, C, and D helices are indicated by dashed lines. 

This mutation in a single codon leads to the change in amino acid sequence at position 6 in the p-chain of human hemoglobin from glutamic acid to valine. The result of this seemingly minor change is sickle cell anemia in individuals who inherit two copies of the mutant gene. 

The alpha chain of human hemoglobin has 141 amino acids in a single polypeptide chain. Calculate the minimum number of bases on DNA necessary to code for the alpha chain. Include in your calculation the bases necessary for specifying the termination of polypeptide synthesis. 

A considerable number of amino acid substitutions have now been described in both the a- and jS-chains of human hemoglobin. Because of the development of knowledge of the amino acid sequence of human hemoglobin, it is possible to correlate symptoms and molecular alterations and in many cases to predict dominant symptomatology on the basis of the molecular distortion, and vice versa. To appreciate this deployment of molecular biology into medicine, some basic concepts of protein structure must be briefly reviewed [12-17]. 

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