Hemoglobin amino acid residues

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

A model for the allosteric behavior of hemoglobin is based on recent observations that oxygen is accessible only to the heme groups of the a-chains when hemoglobin is in the T conformational state. Perutz has pointed out that the heme environment of /3-chains in the T state is virtually inaccessible because of steric hindrance by amino acid residues in the E helix. This hindrance dis-... 

Detection of Variants With Altered Functional Properties. When substitutions In either a-or 3-chains Involve amino acid residues that participate In the contact with heme or the contact between chains, changes In functional properties can occur and the determination of the oxygen affinity of the blood sample or of an Isolated hemoglobin variant Is desirable. Oxygen affinity Is affected by temperature, pH, salt concentration, the level of 2,3-dlphosphoglycerate (2,3-DPG), and to a lesser extent by the concentration of the hemoglobin. The concentration of 2,3-DPG In blood changes rather rapidly after collection and a... 

Normal hemoglobin molecules are complex, three-dimensional structures consisting of four chains of amino acids known as polypeptide chains. Two of these chains are known as alpha subunits with 141 amino acid residues each, and the remaining polypeptide chains are the beta subunits with 146 amino acid residues each. The sequences of amino acids in the alpha and beta subunits are different, but fold up via noncovalent interactions to form similar three-dimensional structures. When a polypeptide chain arranges itself in space, i.e., when it folds, amino acids that were far apart in the chain are brought closer in proximity. The final overall shape of the protein molecule is influenced by (1) the amino acids in the chain, and (2) the interactions that are possible between distant amino acids. 

In adults, hemoglobin (HbA see below) is a heterotetramer consisting of two a-chains and two p-chains, each with masses of 16 kDa. The a- and p-chains have different sequences, but are similarly folded. Some 80% of the amino acid residues form a-helices, which are identified using the letters A-H. 

Within the a2 2 hemoglobin tetramer, the a and /3 subunits (made up of 141 and 146 amino acid residues, respectively) can be thought of as two a/S-dimeric units that are symmetrically positioned about a central cavity ... 

Figure 5.13 indicates locations of mutations that have been shown to produce pathological conditions. The majority of the types of mutations that have been discovered in human hemoglobins have been mutations in which either amino acid residues bear-... 

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

The a-helix is the most abundant secondary structural element, determining the functional properties of proteins as diverse as a-keratin, hemoglobin and the transcription factor GCN4. The average length of an a-helix in proteins is approximately 17 A, corresponding to 11 amino acid residues or three a-helical turns. In short peptides, the conformational transition from random coil to a-helix is usually entropically disfavored. Nevertheless, several methods are known to induce and stabilize a-helical conformations in short peptides, including ... 

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