Myoglobin structure


The first x-ray crystallographic structural results on a globular protein molecule were reported for myoglobin (Figure 2.1) in 1958, and came as a shock to those who had hoped for simple, general principles of protein structure and function analogous to the simple and beautiful double-stranded DNA structure that had been determined five years before by James Watson and Francis Crick. John Kendrew at the Medical Research Council Labora tory of Molecular Biology, in Cambridge, UK, who determined the myoglobin structure to low resolution in 1958, expressed his disappointment about the complexity of the structure in the following words "Perhaps the most remarkable features of the molecule are its complexity and its lack of symmetry. The arrangement seems to be almost totally lacking in the kind of regularities which one instinctively anticipates, and it is more complicated than has been predicted by any theory of protein structure."  [c.13]

J. R. Gunn, A. Monge, R.A. Friesner and G.H. Marshall, Hierarchical algorithm for computer modeling of protein tertiary structure folding of myoglobin to 6.2A resolution, J. Phys. Ghem. 98 (1994), 702-711.  [c.222]

Ideally one could determine the primary structure of even the largest protein by repeating the Edman procedure Because anything less than 100% conversion m any sm gle Edman degradation gives a mixture containing some of the original peptide along with the degraded one two different PTH derivatives are formed m the next Edman cycle and the ideal is not realized m practice Nevertheless some impressive results have been achieved It is a fairly routine matter to sequence the first 20 ammo acids from the N terminus by repetitive Edman cycles and even 60 residues have been determined on a single sample of the protein myoglobin The entire procedure has been automated and incorporated into a device called an Edman sequenator, which carries out all the operations under computer control  [c.1135]

Most protein tertiary structures are determined by X ray crystallography The first myoglobin the oxygen storage protein of muscle was determined m 1957 Since then thousands more have been determined The data are deposited as a table of crystallo graphic coordinates m the Protein Data Bank and are freely available The three dimensional structure of carboxypeptidase A m Figure 27 18 for example was produced by downloading the coordinates from the Protein Data Bank and converting them to a molecular model At present the Protein Data Bank averages about one new protein structure per day  [c.1146]

Most potential energy surfaces are extremely complex. Fiber and Karplus analyzed a 300 psec molecular dynamics trajectory of the protein myoglobin. They estimate that 2000 thermally accessible minima exist near the native protein structure. The total number of conformations is even larger. Dill derived a formula to calculate the upper bound of thermally accessible conformations in a protein. Using this formula, a protein of 150 residues (the approx-  [c.14]

Amino acids (or strictly a-amino acids) are the building blocks of peptides, proteins, and enzymes. Some examples (alanine, phenylalanine, and aspartic acid) are shown in Figure 45.3. Peptides and proteins play key roles in most biological processes. Besides forming structural materials in animate species (hair, muscle, ligaments, etc.), other peptides and proteins and especially enzymes determine the pattern of chemical reactions in cells and mediate many other functions, such as transport and storage of nutrients, immune protection, and the control of growth. For example, hemoglobin transports oxygen in blood, and the related myoglobin transports oxygen in muscle iron is carried in blood plasma by yet another protein, transferrin ovulation is controlled by simple hormonal peptides carbohydrates are broken down into sugars by enzymes.  [c.330]

Many polypeptides also assume helical structures in the crystalline state and—in equilibrium with unwound random conformations-in solution. In this case the helix is stabilized by hydrogen bonding between the N-H and 0=C groups on successive turns of the helix. Fixed bond angles and bond lengths restrict stable helices to those containing either 3.7 or 5.1 repeat units per turn. The former, commonly called the a helix, is shown in Fig. 1.10b it possesses about 18 amino acid residues in every five turns. Many globular proteins, for example, myoglobin, contain helical sections in which the helix is interrupted occasionally, the chain bends through a kink, then the helix resumes. Finally, there is the most famous helical structure of all the DNA double helix. Random coils are not without competition as the structure of polymer molecules  [c.65]

The simplest approach to calculating both AG and X is to assume that the energetics of the redox site and the outer shell can be determined independently (i.e., the energies are uncoupled). Thus, as a first approximation, the change in the energy of the redox site can be calculated from quanmm mechanical calculations of analogs, and the change in the outer shell energy can be calculated from classical calculations. The coupling between the redox site and outer shell energies is through the potential energy parameters, especially the partial charges, of the redox site used in the classical calculations. Because environmental effects due to the protein and/or solvent may influence the electronic structure, a higher order approximation is to use mixed quantum-classical methods (see Chapter 11) such as are used in a study of electronic tunneling pathways in ruthenium-modified myoglobin [6] however, such calculations are not yet routine.  [c.395]

Figure 2.1 Kendrew s model of the low-resolution structure of myoglobin shown in three different views. The sausage-shaped regions represent a helices, which are arranged in a seemingly Irregular manner to form a compact globular molecule. (Courtesy of J.C. Kendrew.) Figure 2.1 Kendrew s model of the low-resolution structure of myoglobin shown in three different views. The sausage-shaped regions represent a helices, which are arranged in a seemingly Irregular manner to form a compact globular molecule. (Courtesy of J.C. Kendrew.)
When high-resolution studies of myoglobin became available, Kendrew noticed that the amino acids in the interior of the protein had almost exclusively hydrophobic side chains. This was one of the first important general principles to emerge from studies of protein structure. The main driving force for folding water-soluble globular protein molecules is to pack hydrophobic side chains into the interior of the molecule, thus creating a hydrophobic core and a hydrophilic surface.  [c.14]

The a helix is the classic element of protein structure. It was first described in 1951 by Linus Pauling working at the California Institute of Technology. He predicted that it was a structure which would be stable and energetically favorable in proteins. He made this remarkable prediction on the basis of accurate geometrical parameters that he had derived for the peptide unit from the results of crystallographic analyses of the structures of a range of small molecules. This prediction almost immediately received strong experimental support from diffraction patterns obtained by Max Perutz in Cambridge, UK, from hemoglobin crystals and keratin fibers. It was completely verified from John Kendrew s high-resolution structure of myoglobin, where all secondary structure is helical.  [c.14]

Figure 2.9 (a) The structure of myoglobin displaying all atoms as small circles connected by straight lines. Even though only side chains at the surface of the molecule are shown, the picture contains so many atoms that such a two-dimensional representation is very confusing and very little information can be gained from it. (b-d) Computer-generated schematic diagrams at different degrees of simplification of the structure of myoglobin, [(a) Half of a stereo diagram by H.C. Watson, Prog. Stereochem. 4 299-333, 1969, by permission of Plenum Press.  [c.22]

Figure 2.10 Examples of schematic diagrams of the type pioneered by Jane Richardson. Diagram (a) illustrates the structure of myoglobin in the same orientation as the computer-drawn diagrams of Figures 2.9b-d. Diagram (b), which is adapted from J. Richardson, illustrates the structure of the enzyme triosephosphate isomerase, determined to 2.5 A resolution in the laboratory of David Phillips, Oxford University. Such diagrams can easily be obtained from databases of protein structures, such as PDB, SCOP or CATH, available on the World Wide Web. Figure 2.10 Examples of schematic diagrams of the type pioneered by Jane Richardson. Diagram (a) illustrates the structure of myoglobin in the same orientation as the computer-drawn diagrams of Figures 2.9b-d. Diagram (b), which is adapted from J. Richardson, illustrates the structure of the enzyme triosephosphate isomerase, determined to 2.5 A resolution in the laboratory of David Phillips, Oxford University. Such diagrams can easily be obtained from databases of protein structures, such as PDB, SCOP or CATH, available on the World Wide Web.
Kendrew, J.C., et al. Structure of myoglobin. Nature 185 422-427, 1960.  [c.33]

The first globular protein structure that was determined, myoglobin, belongs to the class of alpha- (a-) domain structures. The structure illustrated in Figure 2.9 is called the globin fold and is a representative example of one class of a domains in proteins short a helices, the building blocks, are connected by loop regions and packed together to produce a hydrophobic core. Packing interactions within the core hold the helices together in a stable globular structure, while the hydrophilic residues on the surface make the protein soluble in water. In this chapter we will describe some of the different a-domain structures in soluble proteins.  [c.35]

The pairwise arrangements of the sequential a helices in the globin fold are quite different from the antiparallel organization found in the four-helix-bundle a structures. The globin structure is a bundle of eight a helices, usually labeled A-H, connected by rather short loop regions and arranged so that the helices form a pocket for the active site, which in myoglobin and the hemoglobins binds a heme group (Figure 3.10). The lengths of the a helices vary considerably, from 7 residues in the shortest helix (C) to 28 in the longest helix (H) in myoglobin. In the globin fold the a helices wrap around the core in different directions so that sequentially adjacent a helices are usually not adjacent to each other in the structure. The only exceptions are the last two a helices (G and H), which form an antiparallel pair with extensive packing interactions between them. All other packing interactions are formed between pairs of a helices that are not sequentially adjacent. Because the globin fold is not built up from an assembly of smaller motifs, it is quite difficult to visualize conceptually in spite of its relatively small size and simplicity.  [c.40]

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. 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.
Coiled-coil a-helical structures are found both in fibrous proteins and as parts of smaller domains in many globular proteins. Alpha- (a-) domain structures consist of a bundle of a helices that are packed together to form a hydro-phobic core. A common motif is the four-helix bundle structure, where four helices are pairwise arranged in either a parallel or an antiparallel fashion and packed against each other. The most intensively studied a structure is the glo-bin fold, whicn has been found in a large group of related proteins, including myoglobin and hemoglobin. This structure comprises eight a helices that wrap around the core in different directions and form a pocket where the heme group is bound.  [c.45]

Fermi, G., Pemtz, M.F. Atlas of Molecular Structures in Biology. 2. Haemoglobin and Myoglobin. Oxford,  [c.46]

These calculations have shown that collective movements occur on the picosecond time scale for individual residues, and in nanoseconds for loop regions. Such movements are very important for the function of many protein molecules. Reactions such as electron transfer or ligand binding and release occur on these time scales and usually require movements of protein atoms. As soon as the structure of myoglobin was determined it was immediately apparent that the static picture of the myoglobin molecule seen in the crystal did not allow oxygen atoms to enter its binding site or diffuse out. We now know that while the myoglobin molecule is breathing, pathways are opened up between the solvent and the buried binding site to allow oxygen binding or release on a time scale of nanoseconds.  [c.105]

Important novel information has thus been obtained for the specific biological function of those molecules, but disappointingly few general lessons have been learned that are relevant for other membrane-bound proteins with different biological functions. In that respect the situation is similar to the failure of the structure of myoglobin to provide general principles for the construction of soluble protein molecules as described in Chapter 2.  [c.247]

Since there are so few direct packing interactions between protein molecules in a crystal, small changes in, for example, the pH of the solution can cause the molecules to pack in different ways to produce different crystal forms. The structures of some protein molecules such as lysozyme and myoglobin have been determined in different crystal forms and found to be essentially similar, except for a few side chains involved in packing interactions. Because they are so few, these interactions between protein molecules in a crystal do not change the overall structure of the protein. However,  [c.375]

As described in Chapter 2, the first complete protein structure to be determined was the globular protein myoglobin. However, the a helix that was recognized in this structure, and which has emerged as a persistent structural motif in the many hundreds of globular proteins determined subsequently, was first observed in x-ray diffraction studies of fibrous proteins.  [c.384]

Table 5.2 gives the amino acid composition of several selected proteins ribonuclease A, alcohol dehydrogenase, myoglobin, histone H3, and collagen. Each of the 20 naturally occurring amino acids is usually represented at least once in a polypeptide chain. However, some small proteins may not have a representative of every amino acid. Note that ribonuclease (12.6 kD, 124 amino acid residues) does not contain any tryptophan. Amino acids almost never occur in equimolar ratios in proteins, indicating that proteins are not composed of repeating arrays of amino acids. There are a few exceptions to this rule. Collagen, for example, contains large proportions of glycine and proline, and much of its structure is composed of (Gly-x-Pro) repeating units, where x is any amino acid. Other proteins show unusual abundances of various amino acids. For example, histones are rich in positively charged amino acids such as arginine and lysine. Histones are a class of proteins found associated with the anionic phosphate groups of eukaryotic DNA.  [c.113]

FIGURE 5.30 Inspection of the amino acid sequences of the globin chains of human hemoglobin and myoglobin reveals a strong degree of homology. The u-globin and /3-globin chains share 64 residues of their approximately 140 residues in common. Myoglobin and the u-globin chain have 38 amino acid sequence identities. This homology is further reflected in these proteins tertiary structure. (Irving Geis)  [c.146]

Globular proteins exist in an enormous variety of three-dimensional structures, but nearly ail contain substantial amounts of the a-helices and /3-sheets that form the basic structures of the simple fibrous proteins. For example, myoglobin, a small, globular, oxygen-carrying protein of muscle (17 kD, 153 amino acid residues), contains eight a-helical segments, each containing 7 to 26 amino acid residues. These are arranged in an apparently irregular (but invariant) fashion (see Figure 5.7). The space between the helices is filled efficiently and tightly with (mostly hydrophobic) amino acid side chains. Most of the polar side chains in myoglobin (and in most other globular proteins) face the outside of the protein structure and interact with solvent water. Myoglobin s structure is unusual because most globular proteins contain a relatively small amount of a-helix. A more typical globular protein (Figure 6.23) is bovine ribonuclease A, a small protein (14.6 kD, 129 residues) that contains a few short helices, a broad section of antiparallel /3-sheet, a few /3-turns, and several peptide segments without defined secondary structure.  [c.179]

In addition to nonrepetitive but well-defined structures, which exist in all proteins, genuinely disordered segments of polypeptide sequence also occur. These sequences either do not show up in electron density maps from X-ray crystallographic studies or give diffuse or ill-defined electron densities. These segments either undergo actual motion in the protein crystals themselves or take on many alternate conformations in different molecules within the protein crystal. Such behavior is quite common for long, charged side chains on the surface of many proteins. For example, 16 of the 19 lysine side chains in myoglobin have uncertain orientations beyond the S-carbon, and five of these are disordered beyond the /3-carbon. Similarly, a majority of the lysine residues are disordered in trypsin, rubredoxin, ribonuclease, and several other proteins. Arginine residues, however, are usually well ordered in protein structures. For the four proteins just mentioned, 70% of the arginine residues are highly ordered, compared to only 26% of the lysines.  [c.182]

Special Focus Hemoglobin and Myoglobin— Paradigms of Protein Structure and Function  [c.460]

Hemoglobin and Myoglobin—Paradigms of Protein Structure and Function  [c.480]

Before examining myoglobin and hemoglobin in detail, let us first encapsulate the lesson Myoglobin is a compact globular protein composed of a single polypeptide chain 153 amino acids in length its molecular mass is 17.2 kD (Figure 15.23). It contains heme, a porphyrin ring system complexing an iron ion, as its prosthetic group (see Figure 5.15). Oxygen binds to Mb via its heme. Hemoglobin (Hb) is also a compact globular protein, but Hb is a tetramer. It consists of four polypeptide chains, each of which is very similar structurally  [c.480]

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  [c.483]

In any protein structure, the segments of the polypeptide chain that cannot be classified as defined secondary structures, such as helices or sheets, have been traditionally referred to as coil or random coil. Both these terms are misleading. Most of these segments are neither coiled nor random, in any sense of the words. These structures are every bit as highly organized and stable as the defined secondary structures. They are just more variable and difficult to describe. These so-called coil structures are strongly influenced by side-chain interactions. Few of these interactions are well understood, but a number of interesting cases have been described. In his early studies of myoglobin structure, John Kendrew found that the —OFI group of threonine or serine often forms a hydrogen bond with a backbone NIT at the beginning of an a-helix. The same stabilization of an a-helix by a serine is observed in the three-dimensional structure of pancreatic trypsin inhibitor (Figure 6.25). Also in this same structure, an asparagine residue adjacent to a /3-strand is found to form FI bonds that stabilize the /3-structure.  [c.181]

Figure Bl.2.10. Structure of the protohaeme unit found in haemoglobin and myoglobin. Figure Bl.2.10. Structure of the protohaeme unit found in haemoglobin and myoglobin.
The availability of the first protein structures detennined by X-ray crystallography led to the initial view that these molecules were very rigid, an idea consistent with the lock-and-key model of enzyme catalysis. Detailed analysis of protein structures, however, indicated that proteins had to be flexible in order to perfonn their biological functions. For example, in the case of myoglobin and hemoglobin, there is no path for the escape of O2 from the heme-binding pocket in the crystal strucmre the protein must change structure in order for the O2 to be released. This and other realizations lead to a rethinking of the properties of proteins, which resulted in a more dynamic picmre of protein strucmre. Experimental methods have been developed to investigate the dynamic properties of proteins however, the information content from these studies is generally isotropic in namre, affording little insight into the atomic details of these fluctuations [13]. Atomic resolution information on the dynamics of proteins as well as other biomolecules and the relationship of dynamics to function is an area where computational studies can extend our knowledge beyond what is accessible to experimentalists.  [c.2]

Macromolecules in general, and proteins in particular, display a broad range of characteristic motions. These range from the fast and localized motions characteristic of atomic flucmations to the slow large-scale motions involved in the folding transition. Many of these motions, on each and every time scale, have an important role in the biological function of proteins. For example, localized side-chain motion controls the diffusion of oxygen into and out of myoglobin and hemoglobin [1]. A more extensive medium-scale structural transition is involved, for example, in the hemoglobin R to T allosteric transition, which makes it such an efficient transport agent [1]. Finally, prion proteins exliibit a global structural transition of biological importance. These proteins undergo a global transition from an a-helical structure to a predominantly (3-sheet structure, which is implicated in the onset of Creutzfeldt-Jacob disease (CJD) in humans and the mad cow disease in cattle (bovine spongiform encephalopathy BSE) [10].  [c.40]

One of the most important a structures is the globin fold. This fold has been found in a large group of related proteins, including myoglobin, hemoglobins, and the light-capturing assemblies in algae, the phycocyanins. The functional and evolutionary aspects of these structures will not be discussed in this book instead, we will examine some features that are of general structural interest.  [c.40]

Most protein tertiary structures are determined by X-ray crystallography. The first, myoglobin, the oxygen storage protein of muscle, was determined in 1957. Since then thousands more have been determined. The data are deposited as a table of crystallographic coordinates in the Protein Data Bank and are freely available. The three-dimensional structure of carboxypeptidase A in Figure 27.18, for exanple, was produced by downloading the coordinates from the Protein Data Bank and converting them to a molecular- model. At present, the Protein Data Bank averages about one new protein strncture per day.  [c.1146]

FIGURE 5.7 (a) Proteins having structural roles in cells are typically fibrous and often water insoluble. Collagen is a good example. Collagen is composed of three polypeptide chains that intertwine, (b) Soluble proteins serving metabolic functions can be characterized as compactly folded globular molecules, such as myoglobin. The folding pattern puts hydrophilic amino acid side chains on the outside and buries hydrophobic side chains in the interior, making the protein highly water soluble, (c) Membrane proteins fold so that hydrophobic amino acid side chains are exposed in their membrane-associated regions. The portions of membrane proteins extending into or exposed at the aqueous environments are hydrophilic in character, like soluble proteins. Bacteriorhodopsin is a typical membrane protein it binds the light-absorbing pigment, cis-retinal, shown here in red.  [c.116]

The secondary and tertiary structures of myoglobin and ribonuclease A illustrate the importance of packing in tertiary structures. Secondary structures pack closely to one another and also intercalate with (insert between) extended polypeptide chains. If the sum of the van der Waals volumes of a protein s constituent amino acids is divided by the volume occupied by the protein, packing densities of 0.72 to 0.77 are typically obtained. This means that, even with close packing, approximately 25% of the total volume of a protein is not occupied by protein atoms. Nearly all of this space is in the form of very small cavities. Cavities the size of water molecules or larger do occasionally occur, but they make up only a small fraction of the total protein volume. It is likely that such cavities provide flexibility for proteins and facilitate conformation changes and a wide range of protein dynamics (discussed later).  [c.181]

Ancient life forms evolved in the absence of oxygen and were capable only of anaerobic metabolism. As the earth s atmosphere changed over time, so too did living things. Indeed, the production of Og by photosynthesis was a major factor in altering the atmosphere. Evolution to an oxygen-based metabolism was highly beneficial. Aerobic metabolism of sugars, for example, yields far more energy than corresponding anaerobic processes. Two important oxygenbinding proteins appeared in the course of evolution so that aerobic metabolic processes were no longer limited by the solubility of Og in water. These proteins are represented in animals as hemoglobin (Hb) in blood and myoglobin (Mb) in muscle. Because hemoglobin and myoglobin are two of the most-studied proteins in nature, they have become paradigms of protein structure and function. Moreover, hemoglobin is a model for protein quaternary structure and allosteric function. The binding of Og by hemoglobin, and its modulation by effectors such as protons, COg, and 2,3-bisphosphoglycerate, depend on interactions between subunits in the Hb tetramer. Subunit-subunit interactions in Hb reveal much about the functional significance of quaternary associations and allosteric regulation.  [c.480]

FIGURE 15.24 Detailed structure of the myoglobin molecule. The myoglobin polypeptide chain consists of eight helical segments, designated by the letters A through H, counting from the N-terminus. These helices, ranging in length from 7 to 26 residues, are linked by short, unordered regions that are named for the helices they connect, as in the AB region or the EF region. The individual amino acids in the polypeptide are indicated according to their position within the various segments, as in His F8, the eighth residue in helix F, or Phe CDl, the first amino acid in the interhelical CD region. Occasionally, amino acids are specified in the conventional way, that is, by the relative position in the chain, as in Gly. The heme group is cradled within the folded polypeptide chain. (Irving G s)  [c.481]

Lysozyme is a small globular protein composed of 129 amino acids (14 kD) in a single polypeptide chain. It has eight cysteine residues linked in four disulfide bonds. The structure of this very stable protein was determined by X-ray crystallographic methods in 1965 by David Phillips (Figure 16.32). Although X-ray structures had previously been reported for proteins (hemoglobin and myoglobin), lysozyme was the first enzyme structure to be solved by crystallographic (or any other) methods. Although the location of the active site was not obvious from the X-ray structure of the protein alone. X-ray studies of lysozyme-inhibitor complexes soon revealed the location and nature of the active site. Since it is an enzyme, lysozyme cannot form stable ES complexes for structural studies, because the substrate is rapidly transformed into products. On the other hand, several substrate analogs have proven to be good com-  [c.526]


See pages that mention the term Myoglobin structure : [c.213]    [c.130]    [c.1148]    [c.704]    [c.2]    [c.1148]    [c.147]    [c.166]   
Introduction to protein structure (1999) -- [ c.384 ]