Structure, three-dimensional hemoglobin

Figure 3.13 The hemoglobin molecule is built up of four polypeptide chains two a chains and two (3 chains. Compare this with Figure 1.1 and note that for purposes of clarity parts of the a chains are not shown here. Each chain has a three-dimensional structure similar to that of myoglobin the globin fold. In sicklecell hemoglobin Glu 6 in the (3 chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of hemoglobin was determined in 1968 to 2.8 A resolution in the laboratory of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.

Imately 65 X 55 X 50 It Is composed of four polypeptide chains each resembling quite closely the myoglobin chain The three dimensional structure of the subunits Is held together by weak noncovalent bonds The polar amino acid side chains are In contact with the solvent, and the nonpolar residues are located In the Interior of the molecule or In regions which form the contacts between chains The heme group Is located In a pocket In each chain residues In contact with heme are Invariable ( e are the same In different mammalian hemoglobins) and the bonds between heme and chain are hydrophobic Interactions Contacts between like chains (a-a are... 

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. 

Myoglobin and hemoglobin may be the most-studied and best-understood proteins. They were the first proteins for which three-dimensional structures were determined, and our current understanding of myoglobin and hemoglobin is garnered from the work of thousands of biochemists over several decades. Most important, these... 

Computer-generated model of the quaternary structure of hemoglobin, a protein consisting of four interlinked polypeptide chains, each shown in a different color. Computers are important tools for the study of biomolecules, as they help scientists visualize complex three-dimensional structures. 

In spite of the fact that the a and /3 chains of hemoglobin are nonidentical with the myoglobin chain, the three-dimensional structures of all three chains are strikingly similar myoglobins and hemoglobins differ slightly in amino acid composition, depending on the species, but the protein shape remains essentially the same. 

Hemoglobin has quaternary structure as it is made up of four polypeptide chains two a-chains and two (3-chains (a2 32), each with a heme prosthetic group. Despite little similarity in their primary sequences, the individual polypeptides of hemoglobin have a three-dimensional structure almost identical to the polypeptide chain of myoglobin. 

Chemical crosslinking of proteins in combination with mass spectroscopy is often used for the mapping of the three dimensional structures in proteins. An example is the crosslinking of hemoglobin. " The authors also studied the structures of crosslinked neurofibrillary tangles isolated from the brain of an Alzheimer s disease patient. 

Figure 1 Three-dimensional structures of myoglobin and hemoglobin. (a) Deoxymyoglobin from sperm whale (1A6N) and (b) deoxy-hemoglobin from human (IBZO). Black and gray stick molecules are protoheme-lX. Hemoglobm consists of two af dimers, dark and light gray pairs...

Figure 7.13. Conservation of Three-Dimensional Structure. The tertiary structures of human hemoglobin ( a chain).

The three-dimensional structure of hemoglobin is best described as a pair of identical a P dimers (a i P i and (X 2 P 2)... 

This volume has been written for those chemists and biochemists who may never themselves do X-ray diffraction analyses of crystals, but who need to be able to understand the results of such studies on structures of immediate interest to them. The fields of structural biology and chemistry have blossomed in the years since X-ray diffraction was discovered in 1912. For example, the three-dimensional structures of benzene, graphite, the alkali halides, the boron hydrides, the rare gas halides, penicillin, vitamin Bjj, hemoglobin, lysozyme, transfer RNA, and the common-cold rhinovirus have been determined and, in each case, the results have greatly increased our understanding of fundamental chemistry and biochemistry. 

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