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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structure of the ferric form of myoglobin from the mollusc Aplysia limacina has been refined at 1.6 A resolution, by restrained crystallographic refinement methods. The crystallographic R-factor is 0.19. The tertiary structure of the molecule conforms to the common globin fold, consisting of eight alpha-helices. The N-terminal helix A and helix G deviate significantly from linearity. The distal residue is recognized as Val63 (E7), which, however, does not contact the heme directly. Moreover the sixth (distal) co-ordination position of heme iron is not occupied by a water molecule at neutrality, i.e. below the acid-alkaline transition point of A. limacina myoglobin. The heme group sits in its crevice in the conventional orientation and no signs of heme isomerism are evident. The iron atom is 0.26 A out of the porphyrin plane, with a mean Fe-N (porphyrin) distance of 2.01 A. The co-ordination bond to the proximal histidine has a length of 2.05 A, and forms an angle of 4 degrees with the heme normal. A plane containing the imidazole ring of the proximal His intersects the heme at an angle of 29 degrees with the (porphyrin) 4N-2N direction. Inspection of the structure of pH 9.0 indicates that a hydroxyl ion is bound to the Fe sixth co-ordination position.
J Mol Biol 1989 Feb 05
PMID:Aplysia limacina myoglobin. Crystallographic analysis at 1.6 A resolution. 292 16

A procedure to quantitate the immunogenic potential of protein antigens is presented. It is hypothesized that the intrinsic immunogenicity of an accessible region on the protein arises from the overall structural effect of the presence of the particular assemblage of amino acid residues in the given region. Structural parameters previously derived by Grantham [Science 185, 862-864 (1974)] to differentiate the various amino acids are assigned to each residue position. At each point chosen on the molecule, an av. value is computed due to all residues within 8.5 A of this point; it is proposed that this local average is proportional to the immunogenic potential of the region centered at this point. The method can be used to locate the immunodominant regions of a molecule and to compare the antigenicity of related molecules. Test calculations on hen egg-white lysozyme, sperm whale myoglobin and horse cytochrome c show that segments in these molecules, that have been shown in immunochemical studies to possess antigenic activity, are predicted by this method to be immunodominant.
Mol Immunol 1985 Nov
PMID:Quantitation of the immunogenic potential of protein antigens. 300 10

The evidence which suggests that a helper T (Th) cell recognizes a processed form of a soluble protein antigen in association with a class II MHC antigen on the surface of an antigen presenting cell (APC) has raised many questions and much controversy. A major question that remains unanswered is what is the cellular site(s) and mechanism(s) in which such an antigen is handled by an APC. The controversy relates to the issue of whether a protein antigen is required to be processed by an APC before it is presented to a Th cell. A currently favored hypothesis of antigen presentation, which stems mainly from analyses of T cell reactivity to peptides of protein antigens, is that such antigens are internalized by an APC, processed intracellularly, recycled to the cell surface and then presented to Th cells. As a first test of this hypothesis, we reasoned that although it is currently difficult to study the biochemistry of antigen processing, it is possible to study whether a protein antigen is internalized by an APC and recycled to its surface. In this report, colloidal gold conjugates of pork insulin (PI-Au), a tryptic peptide of pork insulin lacking the insulin receptor-binding portion of the molecule (TI-Au), myoglobin (MYO-Au), and apomyoglobin (APO-Au) were used to follow the pathway(s) and kinetics of antigen internalization and recycling in TA3 B hybridoma cells. Transmission electron micrographs of the routes followed by the PI-Au and TI-Au conjugates suggest that these antigens are internalized and recycled to the surface of an antigen presenting cell within 2-4 hr. In contrast, the patterns obtained for MYO-Au and APO-Au suggest that either the internalization of these antigens serves to channel them into a degradative pathway or that the kinetics of recycling of these antigens is slower. The two types of patterns observed may not be mutually exclusive and the purpose of internalization may vary, depending on the nature of the antigen. These data represent the first analysis of the kinetics and pathways of internalization and recycling of an antigen by an APC. It is impossible to formally prove that the pathway we have demonstrated is the one responsible for processing for antigen presentation. Nevertheless, these results support the notion that a protein antigen is handled intracellularly by an APC and recycled to the surface before it is presented to a Th cell.
J Mol Cell Immunol 1988
PMID:Ultrastructural study of internalization and recycling of antigen by antigen presenting cells. 307 24

A new algorithm is introduced for analyzing gene-duplication-independent (orthologous) and gene-duplication-dependent amino acid sequence similarities between proteins of different species. It is based on the calculation of an autocorrelation function D(x) as a Fourier series analogous to that used in crystal analysis by x-ray diffraction. The primary structure of the protein is decomposed into "homopolypeptide-defective sequences" containing identical or similar amino acid residues and vacancies corresponding to the missing amino acid residues. The Fourier transforms F(h) simulating the diffraction patterns of defective linear gratings corresponding to the defective homopolypeptide sequences are calculated. The squared F(h) values are then used as coefficients of Fourier series corresponding to the autocorrelation functions D(x). A peak of D(x) corresponds to a vector of length x, which is the distance between two identical amino acid residues. It is pointed out that optical diffraction methods, instead of computer methods, would also be useful. It is shown through a number of examples that this method allows satisfactory pattern recognition of homologies and internal duplications of an initial segment of the polypeptide chain. In the latter case the value of the above method may be seen from the fact that it detects repeated duplications in proteins such as spinach ferredoxin and myoglobin, for which other methods had either failed or given inconclusive results. The above approach appears most promising for studies of molecular evolution and structure-sequence correlations.
J Mol Evol 1986
PMID:Pattern recognition of sequence similarities in globular proteins by Fourier analysis: a novel approach to molecular evolution. 308 1

In protein crystallography, it has been customary to omit the low-order data in refinement procedures. These data contain, however, important information about the gross features of the unit cell content and particularly the scattering density of the solvent, i.e. solvent structure. In order to use the low-order Bragg reflections, a solvent evaluation procedure has been developed that permits the description of the low-order structure factors (F) as a combination of solvent and protein terms. This permits the use of all observed F values in a least-squares refinement, results in better refinement (lower R factor) and permits easier placement of water and ion locations. Coupled with the measurement of the crystal density by a density-gradient technique, the evaluation of the solvent scattering makes it possible to determine the amount of salt present in the solvent space. For myoglobin crystals grown from solutions containing close to 40% (w/w) ammonium sulfate only 13% (w/w) of salt is present in the solvent space. This is equivalent to seven (ionized) ammonium sulfate molecules, which is larger than the two to three sulfate ions observed in the crystal solvent space by X-ray diffraction.
J Mol Biol 1988 Jun 20
PMID:Solvent effect in protein crystals. A neutron diffraction analysis of solvent and ion density. 317 1

In rat hearts perfused using the Langendorff technique, a cellular release of myoglobin (an index of sarcolemmal damage) was induced in a dose-dependent way by palmitoyl carnitine concentrations exceeding 1.6 microM in the perfusion solution. From 0.7 to 64.5 mmoles palmitoyl carnitine/kg dry wt were taken up by the heart tissues exposed for 30 min to extracellular palmitoyl carnitine concentrations ranging between 0.7 and 100 microM. The steep S-shaped curve relating the cellular myoglobin release provoked by Ca2+ readmission after Ca2+-free perfusion (the calcium paradox) to the perfusion temperature was shifted to lower temperatures by 2 to 3 degrees C in the presence of 1.6 microM palmitoyl carnitine. The loss of myoglobin induced by a mechanical distention of the left ventricular wall during Ca2+-free perfusion was nearly doubled in the presence of 1.6 microM palmitoyl carnitine. Isolated rod-shaped myocytes turned round within 20 min when the extracellular palmitoyl carnitine concentration exceeded 1.6 microM. It is concluded that the presence of palmitoyl carnitine in the perfusion medium at concentrations below those usually adopted in the literature to study the effects of palmitoyl carnitine on the sarcolemmal function induces membrane disruption and exacerbates the membrane damage caused by other factors. The tissue amphiphile content is probably critical to these effects.
J Mol Cell Cardiol 1988 Oct
PMID:Exogenous palmitoyl carnitine and membrane damage in rat hearts. 321 1

In the spectral region 350-800 nm at 4.2 K we measured magnetic circular dichroism (MCD) spectra of the pentacoordinated complex of protcheme with 2-methylimidazole, deoxyleghemoglobin, neutral and alkaline forms of reduced horseradish peroxidase in the equilibrium states, as well as in non-equilibrium states produced by low-temperature photolysis of their carbon monoxide derivatives. Earlier the corresponding results have been obtained for myoglobin, hemoglobin and cytochromes P-450 and P-420. The energies of Fe-N (proximal His) and Fe-N(pyrroles) bonds and their changes upon ligand binding in heme proteins and enzymes were compared with those in the model heme complex thus providing conformational contribution into stereochemistry of the active site. The examples of weak and strong conformational "pressure" on stereochemistry were analysed and observed. If conformational energy contribution into stereochemistry prevails the electronic one the heme stereochemistry remains unchanged on ligand binding as it was observed for leghemoglobin and alkaline horseradish peroxidase. The change of bond energies in myoglobin and hemoglobin on ligand binding are comparable with those in protein free pentacoordinated protoheme, giving an example of weak conformational contribution to heme stereochemistry. The role of protein conformation energy in the modulation of ligand binding properties of heme in leghemoglobin relative to those in myoglobins is discussed. The most striking result were obtained in the study of reduced horseradish peroxidase in the pH region of 6.0-10.2. It was found that such different perturbations as ligand binding and heme-linked ionization of the distal amino acid residue induce identical changes in heme stereochemistry. Neither heme-linked ionization in the carbon monoxide complex nor the geometry of Fe-Co bond affect the heme local structure of photoproducts. These and other findings suggest a very low conformation mobility of horseradish peroxidase whose protein constraints appear to allow only two preferable geometries of specific amino acid residues that form the heme pocket. The role of the two tertiary structure constraints on the heme in the mechanism of horseradish peroxidase function is discussed. It is supposed that one conformation produces a heme environment suitable for two-electron oxidation of the native enzyme to compound I by hydrogen peroxide while another conformation changes the heme stereochemistry in the direction favourable for back reduction of compound I by the substrate to the resting enzyme through two one-electron steps. The switch from one tertiary structure to another is expected to be induced by substrate bind
Mol Biol (Mosk)
PMID:[Contribution of protein conformation to stereochemistry and reactivity of the active center of heme proteins and enzymes. The existence of horseradish peroxidase conformations and their possible role in the catalysis mechanism]. 325 48

The time course of the loss of myoglobin from the rat ventricular myocardium in the early phase of ischemia was studied with the use of an immunohistochemical technique and an image analyzer. The loss of myoglobin, as an index of myocardial injury, was evident in the left ventricular subendocardium as early as 0.5 hr after occlusion of the left main coronary artery. A clear-cut demarcation of the myoglobin-depleted area helped quantification of the injured areas with an image analyzer. The area with depleted myoglobin became transmural and reached maximum after 2 and 3 hr of occlusion, respectively. Electron microscopic observation of the myoglobin-depleted region revealed amorphous dense bodies in the mitochondria, indicating irreversible damage to the myocardial cells. On the other hand, no irreversible changes could be detected with hematoxylin-eosin stain until 6 hr after the start of the ischemia, and the distinction between the reversible and irreversible areas was unclear. We suggest that depletion of myoglobin from the myocardium serves as a marker for irreversible ischemic injury. Quantitative assessment of the injured areas by immunohistochemical staining for myoglobin together with an image analyzer could be of great value for the evaluation of early ischemic myocardial damage.
Exp Mol Pathol 1987 Dec
PMID:Early loss of myocardial myoglobin detected immunohistochemically following occlusion of the coronary artery in rats. 331 39

A 96 picosecond dynamics trajectory of myoglobin with five xenon-probe ligands in internal cavities is examined to study the effect of protein motions on ligand motion and internal cavity fluctuations. Average structural and energetic properties indicate that the simulation is well behaved. The average protein volume is similar to the volume of the X-ray model and the main-chain atom root-mean-square deviation between the X-ray model and the average dynamical structure is 1.25 A. The protein volume oscillates 3 to 4% around the volume of the X-ray structure. These fluctuations lead to changes in the internal free volume and in the size, shape and location of atom-sized cavity features. Transient cavities produced in the simulation have a crucial role in the movement of two of the ligands. One of the ligands escapes to the protein surface, whilst a second ligand travels through the protein interior. Complex gating processes involving several protein residues are responsible for producing the necessary pores through which the ligand passes between transient cavities or packing defects.
J Mol Biol 1988 Jan 05
PMID:Protein-ligand dynamics. A 96 picosecond simulation of a myoglobin-xenon complex. 335 19

The visible absorption spectra of carbonmonoxymyoglobin in the temperature range 300 to 20 K are reported and compared with the analogous spectra of carbonomonoxyhaemoglobin. The temperature dependence of the zeroth, first and second moment of the observed bands is analysed to obtain information on the local dynamics in the proximity of the haem. Contrary to haemoglobin, the first moment of the observed bands in myoglobin is markedly affected by the solvent composition and its value saturates at temperatures at which the solvent undergoes the glass transition. These data indicate that solvent properties influence the haem pocket stereodynamics in myoglobin; moreover, the different behaviour between myoglobin and haemoglobin suggests that the process should involve the surfaces that are buried in the haemoglobin tetramer and exposed to the solvent in myoglobin, and/or the different protein compressibility.
J Mol Biol 1988 Jan 05
PMID:Interaction between external medium and haem pocket in myoglobin probed by low-temperature optical spectroscopy. 335 20


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