Hemoglobin amino acid sequences

Fig. 3. Hemoglobin. Amino acid sequences of human hemoglobin subuniuts a, y and 6. Numbers on the left of each column refer to residues in the a-subunit only. Numbers on the right refer to the residues in subunits p, y and 6. Single letters, A, B, C, etc. refer to helices according to Kendrew s nomenclature (see Figs.4 5 below, and Figs.9 10 in Proteins). Paired letters, AB, CD, etc. refer to nonhelical, interhelical stretches. The number of residues in each region is given as a subscript in the designating letter.

Compare the human hemoglobin amino acid sequence with the chimpanzee, fish and mouse. Record the number of amino acid differences and similarities. Find and reeord the pereent similarity and percent difference. Use the information below. 

Hemoglobin Amino Acid Sequence for Various Vertebrates... 

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

The amino acid sequence in hemoglobin, with 574 units, is known. 

Fig. 6. Terminal capping and lateral bulging of globular domains in the //-solenoid of the hemoglobin protease from E. coli (Otto et al., 2005). The //-solenoid domains are shown in blue and the remaining regions in dark yellow. (A) Ribbon diagram of the 3D structure and (B) linear map of the domain distribution within the amino acid sequence.

Many protein molecules are composed of more than one subunit, where each subunit is a separate polypeptide chain and can form a stable folded structure by itself. The amino acid sequences can either be identical for each subunit (as in tobacco mosaic virus protein), or similar (as in the a and )3 chains of hemoglobin), or completely different (as in aspartate transcarbamylase). The assembly of many identical subunits provides a very efficient way of constructing... 

Since this structure was first proposed, Braunitzer and co-workers have determined the amino acid sequence of rhinoceros hemoglobin (23a). Its allosteric effector site shows only a single substitution compared to that of human hemoglobin—His NA2/8 — Glu—yet ATP lowers its oxygen affinity more than DPG, and GTP lowers it more than ATP, just as in teleost fish (R. Baumann, unpublished observations). This observation supports the hydrogen bond between N-6 of the adenine and Glu NA2 proposed in Fig. 6 in fact it can hardly be explained without that bond. 

The amino acid sequences of the two hemoglobins differ by only four substitutions, of which only one is unique among the bird sequences determined so far (65, 66). This is H2a Pro (greylag goose) - Ala (bar-... 

Powers, D., Amino acid sequencing of Catostomus clarki hemoglobin. ANL-7635. ANL Rep, 1969 287-8. 

Hemoglobinopathies have traditionally been defined as a family of dis orders caused by production of a structurally abnormal hemoglobin molecule, synthesis of insufficient quantities of normal hemoglobin, or, rarely, both. Sickle-cell anemia (HbS), hemoglobin C disease (HbC), and the thalassemia syndromes are representative hemoglobinopathies that can have severe clinical consequences. The first two conditions result from production of hemoglobin with an altered amino acid sequence, whereas the thalassemias are caused by decreased produc tion of normal hemoglobin. 

Although functioning proteins have very specific amino acid sequences, slight variations can often be tolerated. In some cases, however, a slight variation can be disastrous. For example, some people have a version of hemoglobin—a protein found in red blood cells—that has one incorrect amino acid in about 300. That minor error is responsible for sickle-cell anemia, an inherited condition with painful and often lethal effects. The sickle shape characteristic of this disease is shown in Figure 13.19. 

The amino acid sequences of hemoglobins have been extensively altered hy mutation during evolution Data on the umino acid sequences ol the chains from a vanetv of mamma Ii.hi and mliei veiiebruie hemoglobins show thai the sequence can be varied extensively wilhoui drastic change... 

The structural arguments advanced here to explain f oxygen binding by hemoglobin are supported by comparisons of the amino acid sequences of a and j8 chains for a large number of hemoglobins from different species. Data from 60 species of a chains and 66 species of )S chains... 

Primary structure is the amino / ) acid sequence, which controls the shape of the protein and the role the protein serves in the body. Primary Structure Primary structure is the most fundamental of the four structural levels because it is the protein s amino acid sequence that determines its overall shape and function. So crucial is primary structure to function that the change of only one amino acid out of several hundred can drastically alter biological properties. The disease sickle-cell anemia, for example, is caused by a genetic defect in blood hemoglobin whereby valine is substituted for glutamic add at only one position in a chain of 146 amino acids. 

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