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Molecular Aspects of Medicine Apr 2022Antonini and Brunori's 1971 book "Hemoglobin and Myoglobin in Their Reactions with Ligands" was a truly remarkable publication that summarized almost 100 years of... (Review)
Review
Antonini and Brunori's 1971 book "Hemoglobin and Myoglobin in Their Reactions with Ligands" was a truly remarkable publication that summarized almost 100 years of research on O binding to these globins. Over the ensuing 50 years, ultra-fast laser photolysis techniques, high-resolution and time resolved X-ray crystallography, molecular dynamics simulations, and libraries of recombinant myoglobin (Mb) and hemoglobin (Hb) variants have provided structural interpretations of O binding to these proteins. The resultant mechanisms provide quantitative descriptions of the stereochemical factors that govern overall affinity, including proximal and distal steric restrictions that affect iron reactivity and favorable positive electrostatic interactions that preferentially stabilize bound O. The pathway for O uptake and release by Mb and subunits of Hb has been mapped by screening libraries of site-directed mutants in laser photolysis experiments. O enters mammalian Mb and the α and β subunits of human HbA through a channel created by upward and outward rotation of the distal His at the E7 helical position, is non-covalently captured in the interior of the distal cavity, and then internally forms a bond with the heme Fe(II) atom. O dissociation is governed by disruption of hydrogen bonding interactions with His (E7), breakage of the Fe(II)-O bond, and then competition between rebinding and escape through the E7-gate. The structural features that govern the rates of both the individual steps and overall reactions have been determined and provide the framework for: (1) defining the physiological functions of specific globins and their evolution; (2) understanding the clinical features of hemoglobinopathies; and (3) designing safer and more efficient acellular hemoglobin-based oxygen carriers (HBOCs) for transfusion therapy, organ preservation, and other commercially relevant O transport and storage processes.
Topics: Animals; Carbon Monoxide; Hemoglobins; Humans; Kinetics; Ligands; Mammals; Myoglobin; Oxygen
PubMed: 34544605
DOI: 10.1016/j.mam.2021.101024 -
Physical Chemistry Chemical Physics :... Dec 2020All atom molecular dynamic modeling was applied in order to determine water molecule and electrolyte ion concentration profiles around and inside the myoglobin molecule...
All atom molecular dynamic modeling was applied in order to determine water molecule and electrolyte ion concentration profiles around and inside the myoglobin molecule at various pH values. Significant penetration of counter ions into the molecule was confirmed. The electric potential distribution within and outside the molecule was quantitatively described using the non-linear Poisson-Boltzmann (PB) approach. Using this model, calculations were performed, yielding the surface and zeta potential for various physicochemical parameters, comprising pH, the electric permittivity, the ion penetration depth and the protein volume fraction (crowding effect). The theoretical results were used for the interpretation of experimental data acquired under different ionic strengths and temperatures by electrophoretic mobility measurements. It is confirmed that the experimental data are adequately reflected for acidic pH values by the non-linear PB model where the nominal molecule charge was calculated from the H++ model. The deviations occurring for larger pH values were accounted for by considering additional non-electrostatic interactions stemming from the van der Waals and ion-induced dipole forces. In this way, it is both experimentally and theoretically confirmed that the effective charge of the myoglobin molecule in electrolyte solutions is considerably smaller than the nominal, structure-based, predicted charge. As a result, under physiological conditions prevailing, e.g. in skeletal muscles, the effective charge of the myoglobin molecule should practically vanish. One can expect that the approach developed in this work can be applied for predicting charging mechanisms of other protein molecules characterized by an analogous charge vs. pH characteristic, e.g., the SARS-CoV-2 virus spike proteins, and for soft particles with pH responsive characteristics.
Topics: Animals; Electrolytes; Horses; Hydrogen-Ion Concentration; Models, Chemical; Molecular Dynamics Simulation; Myoglobin; Osmolar Concentration; Solutions; Static Electricity
PubMed: 33206736
DOI: 10.1039/d0cp03771k -
The Journal of Biological Chemistry 2021Proteins are the molecular machines of living systems. Their dynamics are an intrinsic part of their evolutionary selection in carrying out their biological functions.... (Review)
Review
Proteins are the molecular machines of living systems. Their dynamics are an intrinsic part of their evolutionary selection in carrying out their biological functions. Although the dynamics are more difficult to observe than a static, average structure, we are beginning to observe these dynamics and form sound mechanistic connections between structure, dynamics, and function. This progress is highlighted in case studies from myoglobin and adenylate kinase to the ribosome and molecular motors where these molecules are being probed with a multitude of techniques across many timescales. New approaches to time-resolved crystallography are allowing simple "movies" to be taken of proteins in action, and new methods of mapping the variations in cryo-electron microscopy are emerging to reveal a more complete description of life's machines. The results of these new methods are aided in their dissemination by continual improvements in curation and distribution by the Protein Data Bank and their partners around the world.
Topics: Adenylate Kinase; Animals; Databases, Protein; Humans; Models, Molecular; Myoglobin; Ribosomes; Structure-Activity Relationship
PubMed: 33961840
DOI: 10.1016/j.jbc.2021.100749 -
Physiological Reports May 2021Myoglobin is an important regulator of muscle and whole-body metabolism and exercise capacity. Caffeine, an activator of the calcium and cyclic AMP (cAMP)/protein kinase...
Myoglobin is an important regulator of muscle and whole-body metabolism and exercise capacity. Caffeine, an activator of the calcium and cyclic AMP (cAMP)/protein kinase A (PKA) pathway, enhances glucose uptake, fat oxidation, and mitochondrial biogenesis in skeletal muscle cells. However, no study has shown that caffeine increases the endogenous expression of myoglobin in muscle cells. Further, the molecular mechanism underlying the regulation of myoglobin expression remains unclear. Therefore, our aim was to investigate whether caffeine and activators of the calcium signaling and cAMP/PKA pathway increase the expression of myoglobin in L6 myotubes and whether the pathway mediates caffeine-induced myoglobin expression. Caffeine increased myoglobin expression and activated the cAMP/PKA pathway in L6 muscle cells. Additionally, a cAMP analog significantly increased myoglobin expression, whereas a ryanodine receptor agonist showed no significant effect. Finally, PKA inhibition significantly suppressed caffeine-induced myoglobin expression in L6 myotubes. These results suggest that caffeine increases myoglobin expression via the cAMP/PKA pathway in skeletal muscle cells.
Topics: Animals; Caffeine; Cell Line; Central Nervous System Stimulants; Cyclic AMP; Muscle Fibers, Skeletal; Myoglobin; Rats
PubMed: 33991466
DOI: 10.14814/phy2.14869 -
Journal of Inorganic Biochemistry Mar 2021Human Islet Amyloid Polypeptide (hIAPP) or amylin, can bind heme and the resultant complexes are prone to generate partially reduced oxygen species (PROS). The formation...
Human Islet Amyloid Polypeptide (hIAPP) or amylin, can bind heme and the resultant complexes are prone to generate partially reduced oxygen species (PROS). The formation of PROS and the related oxidative stress highlight the importance of Heme-hIAPP in the onset and development of Type 2 Diabetes mellitus (T2Dm) in humans. In this study, the interaction of Heme-hIAPP with apomyoglobin (ApoMb) has been investigated using a combination of spectroscopic and electrophoresis techniques. Absorption, resonance Raman data and gel electrophoresis results confirm that ApoMb can uptake heme from Heme-hIAPP and constitute a six-coordinate high-spin ferric heme active site identical to that of myoglobin (Mb). The heme transfer reaction has two distinct kinetic steps. A possible mechanism of this reaction involves heme transfer to the apoprotein in the first step followed by a reorganisation of the protein chain to form the active site of native Mb. Increase in the pH of the reaction medium enhances the rate of the second step of heme transfer. This possibly corresponds to the deprotonation of a propionate side chain of the heme moiety at high pH which facilitates secondary interactions with the conserved distal Lys45 residue of horse heart Mb. Additionally, ApoMb sequesters ligand bound heme from Heme-hIAPP. After the heme transfer reaction, the amount of PROS formed by Heme-hIAPP complex diminishes significantly. This not only potentially diminishes heme-induced toxicity in the pancreatic β-cells but also produces Mb which has well-documented functions throughout the respiratory system and can thereby likely reduce the risks associated with T2Dm.
Topics: Animals; Heme; Humans; Islet Amyloid Polypeptide; Myoglobin
PubMed: 33450674
DOI: 10.1016/j.jinorgbio.2020.111348 -
Annales de Biologie Clinique Apr 2018The clinical biologist plays a role as a consultant for the relevant use of biological examination. Advisory activities of the medical laboratory may help physician in... (Review)
Review
The clinical biologist plays a role as a consultant for the relevant use of biological examination. Advisory activities of the medical laboratory may help physician in diagnosis or therapeutic algorithm, avoiding redundant ordering or useless tests. In this context, we performed a review of literature about the clinically interest of myoglobin assays. The indications of myoglobin's assays appear fairly limited. It is no longer mentioned in the European guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. In patients with rhabdomyolysis myoglobin is neither a diagnostic nor a prognostic criterion. Its interest in predicting the occurrence of acute renal failure is also discussed. The most recent clinico-biological score (such as the McMahon score) do not integrate it. In this context, we decided to stop performing myoglobin assay.
Topics: Acute Kidney Injury; Biomarkers; Diagnostic Tests, Routine; Humans; Myoglobin; Predictive Value of Tests; Rhabdomyolysis
PubMed: 29623882
DOI: 10.1684/abc.2018.1326 -
Journal of the Science of Food and... Nov 2019The Arctic muskox has economic potential as an alternative meat species and is becoming increasingly popular. The present study aimed to determine the primary structure... (Comparative Study)
Comparative Study
BACKGROUND
The Arctic muskox has economic potential as an alternative meat species and is becoming increasingly popular. The present study aimed to determine the primary structure and pseudoperoxidase activity of muskox myoglobin (Mb) compared to cattle and water buffalo myoglobins.
RESULTS
The primary structure of muskox Mb was determined via a matrix-assisted laser desorption ionization-time of flight mass spectrometry-based mapping approach using the sheep Mb as a reference sequence. The muskox Mb consists of 153 amino acid residues and shows 100% identity with sheep Mb, whereas 98.69% and 97.38% identity is found with cattle and water buffalo Mbs, respectively. Muskox Mb has an autoxidation rate (MetMb formation) higher than both cattle and water buffalo Mbs at pH 7.2 (37 °C). Moreover, its pseudoperoxidase activity is higher than both cattle and water buffalo Mbs at pH 7.4 (physiological pH), whereas it is slightly lower than cattle Mb and higher than water buffalo at a lower pH (5.8), corresponding to the conditions in meat.
CONCLUSION
For the first time, the present study reports the purification of myoglobin from muskoxen and, furthermore, a comparative study is conducted on autoxidation and pseudoperoxidase activity with respect to cattle and water buffalo Mbs at both physiological and acid pH. Overall, the results of the current research provide novel information for future studies useful to the meat industry when considering the importance of myoglobin as a principal pigment in meat colour stability. © 2019 Society of Chemical Industry.
Topics: Amino Acid Sequence; Animals; Buffaloes; Cattle; Color; Hydrogen-Ion Concentration; Kinetics; Mass Spectrometry; Meat; Myoglobin; Sequence Alignment; Sheep
PubMed: 31259416
DOI: 10.1002/jsfa.9901 -
European Biophysics Journal : EBJ Oct 2018Analytical band centrifugation (ABC) is a powerful tool for the analysis of macromolecules and nanoparticles. Although it offers several advantages over the...
Analytical band centrifugation (ABC) is a powerful tool for the analysis of macromolecules and nanoparticles. Although it offers several advantages over the sedimentation velocity (SV) experiment like a physical separation of the individual components and the possibility to perform chemical reactions, its analysis is still very restricted. Therefore, we investigated the integration of ABC data as an alternative approach, as this results in data similar to SV, which can then be evaluated by many established evaluation programs. We investigated this method using two different test systems, myoglobin as a biopolymer with significant diffusion and 100 nm polystyrene latex as a large particle with negligible diffusion, and found some limiting issues. These are namely, broadening of the initial boundary by diffusion of the sample, which can be taken into account and the dynamic density gradient between the solvent in the sector and the overlaid solution, which deforms the initial band upon movement through the gradient and is currently not taken into account. We show the influence these two factors have on the evaluation and show that it is possible to calculate the time-dependent change in solvent density and viscosity in the AUC cell using the integrated form of Fick's second law. We conclude that taking the dynamic density gradient into account will open ABC for the sophisticated methods based on the analysis of the whole sedimentation boundary and not just the determination of an average sedimentation coefficient.
Topics: Animals; Centrifugation; Diffusion; Horses; Myoglobin; Polystyrenes
PubMed: 29931388
DOI: 10.1007/s00249-018-1315-1 -
Applied Spectroscopy Jun 2023To facilitate the design of an optical detection system for assessing rabbit meat quality, nine rabbits of different ages, weights, and varieties were used to collect...
To facilitate the design of an optical detection system for assessing rabbit meat quality, nine rabbits of different ages, weights, and varieties were used to collect optical coefficients, compositions, and microstructures from external oblique muscle (EOM) and internal oblique muscle (IOM) samples to research the relationship between them. The results show that rabbit age had a significant influence ( < 0.05) on the absorption coefficient (μ) and the proportion of myoglobin in IOM and EOM, and the older the rabbits are, the greater the μ and the proportion of myoglobin are. Weight also significantly ( < 0.05) influenced the muscle fiber cross-sectional area. The age and weight had a significant ( < 0.05) impact on the reduced scattering coefficient (μ'). The linear fitting results between the relative proportion of myoglobin and the μ showed that the higher the myoglobin content is, the greater the μ is. The linear fitting results between the cross-sectional area of muscle fiber and the μ' showed that the smaller the cross-sectional area of muscle fiber is, the greater the μ' is. These results will be helpful to intuitively understand the working principle of spectral technology in meat quality detection.
Topics: Animals; Rabbits; Myoglobin
PubMed: 36898965
DOI: 10.1177/00037028231166004 -
Journal of Inorganic Biochemistry May 2019Oligomerization of heme proteins is useful for construction of new materials with cooperative and systematic functions; thus, diverse methods have been applied for... (Review)
Review
Oligomerization of heme proteins is useful for construction of new materials with cooperative and systematic functions; thus, diverse methods have been applied for construction of artificial heme protein oligomers. Three-dimensional (3D) domain swapping is a protein oligomerization phenomenon that exchanges the same domain or secondary structural element between molecules. 3D domain swapping was first reported in 1994; since then many proteins have been reported to domain swap. Our research group has been showing that various heme proteins domain swap. We also found that domain swapping of heme proteins occurs at the early stage of protein folding, and utilized it to construct various heme protein assemblies, including nanorings, cages, hetero dimers with different active sites, and a ligand-binding reversible monomer-polymer system. In this review, the basics and applications of domain swapping of heme proteins are summarized.
Topics: Animals; Bacteria; Cell Membrane; Cytochromes c; Fungi; Myoglobin; Protein Domains; Protein Folding; Protein Multimerization
PubMed: 30856457
DOI: 10.1016/j.jinorgbio.2019.03.002