Comparison Between the Amino-Acid Sequences of Sperm Whale Myoglobin and of Human Hæmoglobin

Nature ◽  
1961 ◽  
Vol 190 (4777) ◽  
pp. 670-672 ◽  
Author(s):  
H. C. WATSON ◽  
J. C. KENDREW
Keyword(s):  
Amino Acid ◽  
Sperm Whale ◽  
Amino Acid Sequences ◽  
Human Haemoglobin ◽  
Sperm Whale Myoglobin

The Croonian Lecture, 1968 - The haemoglobin molecule

1969 ◽  
Vol 173 (1031) ◽  
pp. 113-140 ◽  
Keyword(s):  
Amino Acid ◽  
Oxygen Carrier ◽  
Sperm Whale ◽  
Amino Acid Sequences ◽  
Single Chain ◽  
X Ray ◽  
Isomorphous Replacement ◽  
Twofold Symmetry Axis ◽  
The Right ◽  
Sperm Whale Myoglobin

Haemoglobin is the respiratory protein of the red blood cells which carries oxygen from the lungs to the tissues and facilitates, both directly and indirectly, the return transport of carbon dioxide. Mammalian haemoglobin has a molecular weight of 64500 and contains two pairs of polypeptide chains: the α -chains with 141 amino acid residues each and the β -chains with 146. Each chain is combined with one haem. Myoglobin, the oxygen carrier of muscle, is closely related to haemoglobin, but has a simpler constitution: it consists of only one polypeptide chain of 153 residues and a single haem. The amino acid sequences of the myoglobins and haemoglobins of man and of several animals have been determined (Dayhoff & Eck 1968). By means of the method of isomorphous replacement with heavy atoms, X-ray analysis of sperm whale myoglobin at 2·0 Å resolution provided the first solution of the structure of a protein (Kendrew et al . 1960; Watson 1969). All but 21 of its 153 residues form part of helices; over most of their length these helices have conformations closely resembling the right-handed α -helix of Pauling & Corey (1951). The chain is divided into 8 helical segments, separated by corners or non-helical regions. Together these form a kind of basket into which the haem group fits neatly, so that only its propionic acid side-chains protrude into the surrounding liquid (figures 1, 2). X-ray analysis at 5·5 Å resolution showed each chain of horse haemoglobin to be folded in much the same way as the single chain of sperm whale myoglobin. The 4 chains are arranged tetrahedrally, each carrying one haem in a pocket near the protein surface. The chemically identical halves of the molecule are related by a twofold symmetry axis (figure 3, plate 18; Cullis et al . 1962).

The amino acid sequence of human myoglobin and its minor fractions

1974 ◽  
Vol 186 (1084) ◽  
pp. 249-279 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Dimensional Structure ◽  
Human Haemoglobin ◽  
Human Myoglobin ◽  
Main Component ◽  
Haemoglobin Molecule ◽  
Sperm Whale Myoglobin

The complete amino acid sequence of human skeletal myoglobin is described. That of heart myoglobin is found by homology to be the same. When myoglobin is prepared some minor fractions may be obtained besides the main component. They are shown to be artefacts arising from deamidations. The likely three-dimensional structure of human myoglobin is discussed, taking that of sperm-whale myoglobin as a reference. Human myoglobin is compared with the α - and β -chains of human haemoglobin. There is a noteworthy similarity of internal residues and haem contacts, but little resemblance of sites where the haemoglobin chains form dimeric and tetrameric contacts, when they become subunits of the haemoglobin molecule.

scholarly journals The immunological activity of some of the chymotryptic peptides of sperm-whale myoglobin

1965 ◽  
Vol 94 (3) ◽  
pp. 545-556 ◽  
Author(s):  
MJ Crumpton ◽  
JM Wilkinson
Keyword(s):  
Amino Acid ◽  
Antigenic Site ◽  
Molecular Size ◽  
Sperm Whale ◽  
Exchange Chromatography ◽  
Amino Acid Sequences ◽  
Molecular Weights ◽  
Molar Ratios ◽  
A Minor ◽  
Sperm Whale Myoglobin

1. Sperm-whale apomyoglobin was digested with chymotrypsin in a dialysis sac. The ultrafiltrate contained incompletely hydrolysed fragments which partially inhibited the precipitation of metmyoglobin and apomyoglobin by some antisera produced against metmyoglobin. The inhibitory activity was stable to heating at 100 degrees and depended on the peptide structure. 2. The fragments were fractionated according to molecular size and were purified by ion-exchange chromatography. Six pure peptides and two peptides which contained a minor impurity were isolated. Their amino acid compositions and N-terminal amino acid sequences were determined and their entire amino acid sequences deduced from the known amino acid sequence of sperm-whale myoglobin. 3. The peptides formed no detectable precipitates with the antisera. Five of the eight peptides partially inhibited the precipitation of apomyoglobin and/or metmyoglobin by one antiserum. Six of the peptides inhibited the precipitation of apomyoglobin by one or other of two antisera; at least two of these peptides inhibited both antisera. One peptide failed to inhibit the precipitation of either antigen by either antiserum. Two of the peptides possessed the same serological specificity. 4. The molar ratios of inhibitors to antigen for 50% of the maximum inhibition decreased as the molecular size of the inhibitor increased. With one antiserum and with apomyoglobin as the antigen, molar ratios 12 and 80 were obtained for peptides with molecular weights 2051 and 793 respectively. 5. The size and structure of an antigenic site is discussed in relation to the known steric configuration of myoglobin.

The Amino-Acid Sequence of Sperm Whale Myoglobin: Chemical Studies

Nature ◽  
1961 ◽  
Vol 190 (4777) ◽  
pp. 663-665 ◽  
Author(s):  
A. B. EDMUNDSON ◽  
C. H. W. HIRS
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sperm Whale ◽  
Chemical Studies ◽  
Sperm Whale Myoglobin

The structure of haemoglobin. IX. A three-dimensional Fourier synthesis at 5.5 Å resolution: description of the structure

1962 ◽  
Vol 265 (1321) ◽  
pp. 161-187 ◽  
Keyword(s):  
Tertiary Structure ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Anomalous Scattering ◽  
Fourier Synthesis ◽  
Human Haemoglobin ◽  
Contour Maps ◽  
To Come ◽  
Polypeptide Chains ◽  
Sperm Whale Myoglobin

The electron density distribution in the unit cell is calculated at intervals of approximately 2Å and plotted in a series of sections parallel to (010). The contour maps show that haemoglobin consists of four subunits in a tetrahedral array. The subunits are identical in pairs in accordance with the twofold symmetry of the molecule. The two pairs are very similar in structure, and the members of each pair closely resemble the molecule of sperm-whale myoglobin. The four haem groups lie in separate pockets at the surface of the molecule. The positions of the iron atoms are confirmed by comparison of observed and calculated anomalous scattering effects, which also serve to determine the absolute configuration of the molecule. The four subunits found by X-ray analysis correspond to the four polypeptide chains into which haemoglobin can be divided by chemical methods. In horse haemoglobin the amino acid sequence within these chains is still partly unknown, but in human haemoglobin it has already been determined. Comparison of this sequence with the tertiary structure of the chains as now revealed in horse haemoglobin and with the atomic model of sperm-whale myoglobin recently obtained by Kendrew and his collaborators shows many interesting relations. Prolines appear to come where the chains turn corners or where their configuration is known to be non-helical. On the other hand, the chains also have corners which contain no proline. Certain residues appear to be structurally vital, because they appear in identical positions in myoglobin and in the two chains of haemoglobin, while in other parts of the molecule a wide variety of different side-chains appears to be allowed.

Amino-Acid Sequence of Sperm Whale Myoglobin

Nature ◽  
1965 ◽  
Vol 205 (4974) ◽  
pp. 883-887 ◽  
Author(s):  
ALLEN B. EDMUNDSON
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sperm Whale ◽  
Sperm Whale Myoglobin

scholarly journals Primary structure of a dimeric haemoglobin from the deep-sea cold-seep clam Calyptogena soyoae

1989 ◽  
Vol 260 (1) ◽  
pp. 177-182 ◽  
Author(s):  
T Suzuki ◽  
T Takagi ◽  
S Ohta
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Amino Acid Sequences ◽  
Cold Seep ◽  
Intact Protein ◽  
British Library ◽  
Amino Acid Residues ◽  
Sagami Bay ◽  
Human Haemoglobin ◽  
Subunit Assembly

The heterodont clam Calyptogena soyoae, living in the cold-seep area of the upper bathyal depth of Sagami Bay, Japan, has two homodimeric haemoglobins (Hb I and Hb II) in erythrocytes. The complete amino acid sequence of 136 residues of C. soyoae Hb II was determined. The sequence showed low homology with any other globins (at most 20% identity) and lacked the N-terminal extension of seven to nine amino acid residues characteristic of all the molluscan haemoglobins sequenced hitherto. Although the subunit assembly of molluscan haemoglobin is known to be ‘back-to-front’ relative to vertebrate haemoglobin, C. soyoae Hb II is unlikely to undergo such a subunit assembly because it lacks homology in the sequence involving subunit interaction. These structural features suggest that C. soyoae haemoglobin may have accomplished a unique molecular evolution. The distal (E7) histidine residue of C. soyoae Hb II is unusually replaced by glutamine. However, the oxyhaemoglobin is stable enough to act as an O2 carrier, since the autoxidation rate at near physiological temperature (3 degrees C) is about 3 times lower than that of human haemoglobin at 37 degrees C. H.p.l.c. patterns of peptides (Figs. 5-7), amino acid compositions of intact protein and peptides (Table 1) and amino acid sequences of intact protein and peptides (Tables 2 and 3) have been deposited as Supplementary Publication SUP 50150 (11 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1989) 257, 5.

scholarly journals Prediction and conformation by synthesis of two antigenic sites in human haemoglobin by extrapolation from the known antigenic structure of sperm-whale myoglobin

1977 ◽  
Vol 167 (1) ◽  
pp. 275-278 ◽  
Author(s):  
A L Kazim ◽  
M Z Atassi
Keyword(s):  
Sperm Whale ◽  
Antigenic Structure ◽  
Homologous Proteins ◽  
Human Haemoglobin ◽  
Antigenic Sites ◽  
Inductive Effects ◽  
Structural Analogy ◽  
Starting Model ◽  
Sperm Whale Myoglobin

The complete antigenic structure of sperm-whale myoglobin was previously determined in our laboratory. By structural analogy with myoglobin, two regions in human haemoglobin were predicted to comprise antigenic sites. One region was on the alpha-chain [alpha-(15-23)] and the other on the beta-chain [beta-(16-23)]. These two regions were synthesized, purified and characterized, and their immunochemistry was studied. Each peptide was able specifically to bind considerable amounts of haemoglobin antibodies. In a set of homologous proteins, barring any drastic conformational or electrostatic inductive effects exerted by the substitutions, and allowing for obstruction due to subunit interaction, the determination of the antigenic structure of one protein may serve as a useful starting model for the others.

scholarly journals The antibody response to myoglobin is independent of the immunized species. Analysis in terms of replacements in the antigenic sites and in environmental residues of the cross-reactions of fifteen myoglobins with sperm-whale myoglobin antisera raised in different species

1980 ◽  
Vol 191 (3) ◽  
pp. 681-697 ◽  
Author(s):  
S S Twining ◽  
H Lehmann ◽  
M Z Atassi
Keyword(s):  
Amino Acid ◽  
Antibody Response ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Cross Reactivity ◽  
Antigenic Structure ◽  
Amino Acid Substitutions ◽  
Antigenic Sites ◽  
The Cross ◽  
Sperm Whale Myoglobin

The recent determination of the entire antigenic structure of sperm-whale myoglobin with rabbit and goat antisera has permitted the examination of whether the antigenic structure recognized by antibodies depends on the species in which the antisera are raised. Also, by knowledge of the antigenic structure, the molecular factors that determine and influence antigenicity can be better understood in terms of the effects of amino acid substitutions occurring in the antigenic sites and in the environmental residues of the sites. In the present work, the myoglobins from finback whale, killer whale, horse, chimpanzee, sheep, goat, bovine, echidna, viscacha, rabbit, dog, cape fox, mouse and chicken were examined for their ability to cross-react with antisera to sperm-whale myoglobin. By immunoadsorbent titration studies with radioiodinated antibodies, each of these myoglobins was able to bind antibodies to sperm-whale myoglobin raised in goat, rabbit, chicken, cat, pig and outbred mouse. It was found that the extent of cross-reaction of a given myoglobin was not dependent on the species in which the antisera were raised. This indicated that the antibody response to sperm-whale myoglobin (i.e. its antigenic structure) is independent of the species in which the antisera are raised and is not directed to regions of sequence differences between the injected myoglobin and the myoglobin of the immunized host. Indeed, in each antiserum from a given species examined, that antiserum reacted with the myoglobin of that species. The extent of this auto-reactivity for a given myoglobin was comparable with the general extent of cross-reactivity shown by that myoglobin with antisera raised in other species. The cross-reactivities and auto-reactivities (both of which are of similar extents for a given myoglobin) can be reasonably rationalized in terms of the effects of amino acid substitutions within the antigenic sites and within the residues close to these sites. These findings confirm that the antigenicity of the sites is inherent in their three-dimensional locations.

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