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

The heme vinyl substituents in a shark (Galeorhinus japonicus) myoglobin in its met-cyano form (MbCN) have been characterized by NMR and the results were compared with those of the well-studied sperm whale (Physter catodon) myoglobin. Their orientation has been inferred from NOE connectivities and the analysis of the hyperfine shifts based on the principal magnetic tensor determined by MATDUHM (Magnetic Anisotropy Tensor Orientation Determination Utilizing the Heme Methyls) [Yamamoto, Y., Nanai, N. and Chujo, R.(1990) J. Chem. Soc., Chem. Commun. 1556-1557]. It has been shown that the C3-vinyl group is oriented roughly orthogonal to the heme plane in both G. japonicus and P. catodon MbCNs at 35 degrees C and their C8-vinyl groups, on the other hand, are close to in-plane orientation. Although CO form of myoglobin (MbCO) and MbCN have been thought to be isostructural to each other, the C8-vinyl orientation for P. catodon MbCN is found to be different from the orthogonal orientation indicated in the crystal structure analysis of MbCO [Hanson, J.C. and Schoenborn, B.P. (1981) J. Mol. Biol. 153, 117-146]. Their mobility has been characterized quantitatively from the study of time-dependent NOE build-up between the selected pair of the vinyl proton resonances. It has been revealed that the heme C3- and C8-vinyl groups of approximately 1 mM G. japonicus MbCN at 45 degrees C undergo internal motion with the correlation time of 1.9 and 2.4 ns, respectively. Therefore, their oscillatory motion is faster by a factor of 4-5 compared with the protein overall tumbling. Difference in the internal mobility between the two vinyl groups in the active site of this Mb is attributed to their differential contact with the apo-protein.
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PMID:Orientation and mobility of the heme vinyl groups in myoglobins with the aid of NOE and MATDUHM NMR. 156 83

A combined one-dimensional nuclear Overhauser effect, paramagnetic-induced relaxation and two-dimensional sequence-specific 1H n.m.r. assignment of the spectrum of portions of the distal pocket of Aplysia cyano metMyoglobin (metMbCN) has been carried out in order to establish the presence and identity of distal residues in the heme pocket. In the absence of the usual distal E7 His in Aplysia Mb (E7 Val), the sequence-specific assignment of the E7 and E10 residues, together with their hyperfine shift patterns, relaxivities and dipolar connectivities to each other and the remainder of the E helix, reveal that the E10 Arg is turned into the pocket and hydrogen bonds to the bound cyanide group. We have previously found a similar rearrangement of the E10 Arg in Aplysia fluoro metMyoglobin, and the stabilizing effect of this residue was proposed to be responsible for the slow rate of cyanide dissociation from rapidly reduced ferrous Aplysia myoglobin. Based on the similar distal E7 His hydrogen-bonding interaction to the bound ligand in the crystal of sperm whale MbO2 and in solution of its cyano met complex, we propose that the E10 Arg similarly hydrogen bonds to the bound O2 in Aplysia MbO2 and accounts for its strong ligand binding and slow dissociation rate.
J Mol Biol 1992 Apr 20
PMID:Solution 1H nuclear magnetic resonance determination of hydrogen bonding of the E10 (66) Arg side-chain to the bound ligand in Aplysia cyano-met myoglobin. 156 77

Important properties of globular proteins, such as the stability of the folded state, depend sensitively on interactions with solvent molecules. An excluded volume approximation to protein-solvent interaction, the solvent contact model, was used to derive atomic solvation preference parameters from a database of known protein structures. The ability of solvation preference to discriminate between correct and incorrect three-dimensional structures for a given sequence, or to identify the correct sequence placement in a given structure, was tested. Backbone co-ordinates were taken from experimentally known structures or hypothetical models and side-chain conformations (in rotamer space) were optimized by an efficient Monte Carlo algorithm using simulated annealing and simple potential functions. Discrimination by solvation preference was very clear between deliberately misfolded and correct globular models as well as between native-like and non-native-like topologies of combinatorially generated myoglobin models. Due to its statistical nature, the evaluation works best on entire protein models, while the identification of incorrect parts of models is more difficult. In one case locally incorrect chain tracing in a crystal structure was identified. The method is computationally fast compared to methods based on surface area calculations and is recommended for use as a diagnostic tool in model building based on sequence similarity, in folding simulations and in protein design.
J Mol Biol 1992 May 05
PMID:Evaluation of protein models by atomic solvation preference. 158 96

Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 degrees C) or hypothermic ischemia (5 degrees C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37 degrees C or 5 degrees C and were then reperfused for 15 min at 37 degrees C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 degrees C as compared to 37 degrees C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2- at 5 degrees C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 degrees C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals.
Mol Cell Biochem 1992 Apr
PMID:Reduced free radical generation during reperfusion of hypothermically arrested hearts. 158 48

The 1H nuclear magnetic resonance spectral characteristics of the cyano-Met form of Chironomus thummi thummi monomeric hemoglobins I, III and IV in 1H2O solvent are reported. A set of four exchangeable hyperfine-shifted resonances is found for each of the two heme-insertion isomers in the hyperfine-shifted region downfield of ten parts per million. An analysis of relaxation, exchange rates and nuclear Overhauser effects leads to assignments for all these resonances to histidine F8 and the side-chains of histidine E7 and arginine FG3. It is evident that in aqueous solution, the side-chain from histidine E7 does not occupy two orientations, as found for the solid state, rather the histidine E7 side-chain adopts a conformation similar to that of sperm whale myoglobin or hemoglobin A, oriented into the heme pocket and in contact with the bound ligand. Evidence is presented to show that the allosteric transition in the Chironomus thummi thummi hemoglobins arises from the "trans effect". An analysis of the exchange with bulk solvent of the assigned histidine E7 labile proton confirms that the group is completely buried within the heme pocket in a manner similar to that found for sperm whale cyano-Met myoglobin, and that the transient exposure to solvent is no more likely than in mammalian myoglobins with the "normal" distal histidine orientation. Finally, a comparison of solvent access to the heme pocket of the three monomeric C. thummi thummi hemoglobins, as measured from proton exchange rates of heme pocket protons, is made and correlated to binding studies with the diffusible small molecules such as O2.
J Mol Biol 1991 Oct 05
PMID:Proton nuclear magnetic resonance study of the solution distal histidine orientation in monomeric Chironomus thummi thummi cyanomet hemoglobins. Dynamic stability of the heme pocket as monitored by labile proton exchange. 165 31

Mini-myoglobin, obtained by limited proteolysis of horse heart myoglobin (residues 32 to 139), represents a good model for testing the correlation between an exon and a protein domain. We have shown that ligand binding kinetics, spectral and folding features of mini-myoglobin are very similar to those of native myoglobin. In order to develop further the analysis of the structure-function relationship in this mini-protein, mini-globin was reconstituted with the heme moiety in which iron is replaced by cobalt. The Soret absorption spectra of oxy and deoxy cobaltous mini-myoglobin are very similar to those of cobaltous myoglobin derivatives; in addition. Co-mini-myoglobin binds oxygen reversibly with an n value approximately 1 and a p50 value of 45 to 50 mm Hg (the same as Co-myoglobin). Oxy Co-mini-myoglobin shows a well-resolved electron paramagnetic resonance (e.p.r.) spectrum typical of an oxygenated hemoprotein, while the spectrum of the deoxy derivative, although similar to that of deoxy Co-myoglobin, displays a lower resolution of the complex hyperfine structure. Moreover, photodissociation experiments on oxy Co-mini-myoglobin allow e.p.r. detection of an intermediate state, already observed in most hemoproteins and diagnostic for the interaction of bound oxygen with the distal histidine residue. Thus, reconstitution of mini-globin with cobalt protoprophyrin IX has provided, for the first time, a stable oxygenated complex that reflects a correct folding of the protein surrounding the heme pocket and possesses the functional behaviour typical of a hemoprotein.
J Mol Biol 1991 Dec 05
PMID:Mini-myoglobin. Electron paramagnetic resonance and reversible oxygenation of the cobalt derivative. 166 Sep 28

Analysis of thermodynamic data on the dissolution of solid cyclic dipeptides into water in terms of group additivity provides a rationale for the enthalpy and entropy convergence temperatures observed for small globular protein denaturation and the dissolution of model compounds into water. Convergence temperatures are temperatures at which the extrapolated enthalpy or entropy changes for a series of related compounds take on a common value. At these temperatures (TH* and TS*) the apolar contributions to the corresponding thermodynamic values (delta H degrees and delta S degrees) are shown to be zero. Other contributions such as hydrogen bonding and configurational effects can then be evaluated and their quantitative effects on the stability of globular proteins assessed. It is shown that the denaturational heat capacity is composed of a large positive contribution from the exposure of apolar groups and a significant negative contribution from the exposure of polar groups in agreement with previous results. The large apolar contribution suggests that a liquid hydrocarbon model of the hydrophobic effect does not accurately represent the apolar contribution to delta H degrees of denaturation. Rather, significant enthalpic stabilizing contributions are found to arise from peptide groups (hydrogen bonding). Combining the average structural features of globular proteins (i.e. number of residues, fraction of buried apolar groups and fraction of hydrogen bonds) with their specific group contributions permits a first-order prediction of the thermodynamic properties of proteins. The predicted values compare well with literature values for cytochrome c, myoglobin, ribonuclease A and lysozyme. The major thermodynamic features are described by the number of peptide and apolar groups in a given protein.
J Mol Biol 1991 Dec 05
PMID:Solid model compounds and the thermodynamics of protein unfolding. 166 Sep 31

Most known helper T cell (Th) epitopes studied have naturally been immunodominant epitopes recognized by T cells from animals of high responder major histocompatibility complex (MHC) haplotype. We have previously found that most such immunodominant Th epitopes tend to be amphipathic alpha helices, that is, helices with hydrophobic residues on one side and hydrophilic residues on the other, and the corresponding peptide can usually elicit a response to the native protein. However, very few epitopes seen by MHC low responder T cells have been identified. Within the CNBr fragment of residues 1-55 of sperm whale myoglobin (SwMb), a Th epitope is known to exist that stimulates T cells from low responder H-2k mice, but it has not yet been localized to a length of 8-12 residues, the usual length of a Th epitope. To determine whether this low responder epitope would have similar properties, we located it using 10 evenly overlapping 15-residue peptides that span the region. Analysis of this region by the computer program predicted the site covered by two peptides (residues 26-40 and 31-45 which overlap by 10 residues) to be the most likely site for a Th epitope. Of the 10 peptides tested experimentally, only one peptide (residues 26-40) was able to stimulate two low responder Th clones that are specific for the 1-55 region. The peptide was able to prime T cells of low responder B10.BR mice in vivo for in vitro response to the native SwMb as well as to the peptide fragment of residues 1-55. Immunization of low responder mice with SwMb showed that, of the 10 overlapping peptides, the major site of response within the 1-55 region is to the identified peptide. Finally, an extended peptide of residues 24-42 was made to increase the amphipathic score. This extended peptide induced greater proliferation of the clones. Thus, this low responder epitope has properties similar to those of immunodominant epitopes recognized by high responders.
Mol Immunol 1990 Oct
PMID:Characterization of a helper T cell epitope recognized by mice of a low responder major histocompatibility type. 170 Feb 86

The folding/unfolding transition of proteins is a highly co-operative process characterized by the presence of very few or no thermodynamically stable partially folded intermediate states. The purpose of this paper is to present a thermodynamic formalism aimed at describing quantitatively the co-operative folding behavior of proteins. In order to account for this behavior, a hierarchical algorithm aimed at evaluating the folding/unfolding partition function has been developed. This formalism defines the partition function in terms of multiple levels of interacting co-operative folding units. A co-operative folding unit is defined as a protein structural element that exhibits two-state folding/unfolding behavior. At the most fundamental level are those structural elements that behave co-operatively as a result of purely local interactions. Higher-order co-operative folding units are formed through interactions between different structural elements. The hierarchical formalism utilizes the crystallographic structure of the protein as a template to generate partially folded conformations defined in terms of co-operative folding units. The Gibbs free energy of those states and their corresponding statistical weights are then computed using experimental energetic parameters determined calorimetrically. This formalism has been applied to the case of myoglobin. It is shown that the hierarchical partition function correctly predicts the presence, energetics and co-operativity of the heat and cold denaturation transitions. The major contribution to the co-operative folding behavior arises from the solvent exposure of non-polar residues located in regions complementary to those that have undergone unfolding. This entropically uncompensated and energetically unfavorable solvent exposure characterizes all partially folded states but not the unfolded state, thus minimizing the population of partially folded intermediates throughout the folding/unfolding transition.
J Mol Biol 1991 Dec 05
PMID:Molecular basis of co-operativity in protein folding. 174 98

It has been shown that the distribution of presently known protein loop lengths is consistent with even the simplest available theory of rubber-like elasticity, and with the idea that such loops generate an entropically derived end-to-end tension. It has also been asserted that the molten globule phase, just like the native form, must be mechanically stable, and that a simple demonstration of the potential for mechanical stability would be a powerful test in predictions of new protein folds. This paper amplifies this suggestion by explicit calculation of a familiar but non-trivial test case: sperm-whale myoglobin. The method used is to describe the protein molecule in terms of a highly simplified mechanical model bearing some resemblance to a pre-stressed mechanism. The alpha-helices are treated as rigid rods and the loops are treated as elastic strings. The entropic tensions exerted by the loops are imposed on the mechanism using an approximation proposed earlier. The helices are then held to generate frictionless reaction forces at their mutual points of contact. These contact forces are calculated to null out maximally the effects of the loop tensions, and hence stabilize the molecule. It is shown that the crystallographically determined structure of myoglobin has a significantly higher mechanical stability on this model than does any of a previously published set of combinatorially generated predictions. Amongst the predictions alone, the best is also the one with the highest stability. It is anticipated that this result could be of general importance in sorting or filtering out bad predictions. A further exciting feature of the model is that it offers a natural explanation for the strong conservation of the C2 proline and the invariably long unconserved sequence from the end of the C helix to the start of the E helix in the globins and phycocyanins.
J Mol Biol 1991 Dec 05
PMID:A simplified mechanical model of proteins tested on the globin fold. 174 1


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