Thermodynamic Puzzle of Apomyoglobin Unfolding

Griko, Yuri V.; Privalov, Peter L.

doi:10.1006/jmbi.1994.1085

Cited by 143 publications

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“…Similar non-two-state behavior has been observed with apomyoglobin [5] and staphylococcal nuclease [6]. These proteins show an asynchronous disappearance of tertiary and secondary structure with decreasing pH.…”

Section: Introductionsupporting

confidence: 72%

Acid induced equilibrium unfolding of annexin V wild type shows two intermediate states

et al. 1998

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Annexin V is an K K-helical protein which shows anticoagulatory and antiinflammatory activity. It is supposed to be involved in membrane fusion and exocytosis. In this study acid-induced equilibrium unfolding of the human annexin V is investigated by fluorescence and circular dichroism spectroscopy. The spectroscopic data indicate that at least two intermediate states are involved in unfolding. One of the proposed intermediate states exhibits properties similar to those observed with annexin V wild type saturated with calcium, another may be regarded as`molten globule'.z 1998 Federation of European Biochemical Societies.

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Section: Introductionsupporting

confidence: 72%

Acid induced equilibrium unfolding of annexin V wild type shows two intermediate states

et al. 1998

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“…The conformation of holomyoglobin is similar to that of apomyoglobin by several criteria (Hughson et al, 1990; Griko & Privalov, 1994;Eliezer & Wright, 1996). Therefore, one can compare data available for the apo form of myoglobin to our results.…”

Section: Analysis Of the Simulation Results: Changes In Secondaq Strumentioning

confidence: 89%

Effects of pressure on the structure of metmyoglobin: Molecular dynamics predictions for pressure unfolding through a molten globule intermediate

et al. 1998

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We investigated the pathway for pressure unfolding of metmyoglobin using molecular dynamics (MD) for a range of pressures (0.1 MPa to 1.2 GPa) and a temperature of 300 K. We find that the unfolding of metmyoglobin proceeds via a two-step mechanism native + molten globule intermediate + unfolded, where the molten globule forms at 700 MPa. The simulation describes qualitatively the experimental behavior of metmyoglobin under pressure. We find that unfolding of the alpha-helices follows the sequence of migrating hydrogen bonds (i,i + 4) + (i,i + 2).Keywords: molecular dynamics; molten globule; myoglobin; pressure; unfolding The effect of pressure on chemical and biological systems can lead to improved understanding of the fundamental interactions and to improved processes. Thus, high pressure has been used in food sterilization, extraction procedures, bioconversion using barophilic microorganisms, and enzymology under supercritical conditions (Balny et al., 1992). In addition, microbiology under deep-sea high pressure conditions offers biotechnological opportunities and may provide insights into the origin of life. Microorganisms in the deep-sea live at high pressures (1 10 MPa at 10,660 m) at both low and high temperature and in darkness (Yayanos, 1995).Experimental techniques such as optical spectroscopy, Raman scattering, and NMR have been used to observe pressure effects on proteins (Weber & Drickamer, 1983;Frauenfelder et al., 1990;Jaenicke, 1991;Silva & Weber, 1993;Gross & Jaenicke, 1994 . The pressure denaturation of monomeric proteins, the dissociation of oligomers, and the effects of pressure on macromolecular assemblages have provided insights into the microscopic mechanism of protein folding and the role of solvent in this process (Zipp & Kauzmann, 1973;Li et al., 1976;Chryssomallis et al., 1981;Weber & Drickamer, 1983;Silva et al., 1986;Silva & Weber, 1993;Weber, 1993;Dufour et al., 1994;Peng et al., 1994;Schulte et al., 1995;Silva et al., 1996). These effects are often reversible but can show different degrees of hysteresis.Despite this progress, the detailed atomistic changes involved in pressure transformations have not been well characterized. To provide such information we carried out molecular dynamics (MD) simulations on metmyoglobin as a function of applied external pressure. We selected myoglobin since its folding mechanism and protein folding intermediates have been studied experimentally by many techniques. We find that the applied pressure perturbs the native structure of the protein, eventually destabilizing to denature the molecule. By examining the conformation of the intermediates from the MD, we determined the pathway for unfolding. The results are in agreement with the experiment. 2301

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“…Its structure differs from that of holomyoglobin by the position of its loops and helices, with one of the latter, F-helix, being completely destroyed, [12][13][14] and the total helicity being reduced from 78% to 65%. 15 Nevertheless, apoMb holds its hydrophobic core 16 and a peculiar holomyoglobin-like tertiary structure. 17 According to the thermodynamic criteria, when heated, both holomyoglobin and its apo-form undergo cooperative denaturing transitions accompanied by notable changes in their enthalpy and heat capacity.…”

Section: Introductionmentioning

confidence: 99%

How strong are side chain interactions in the folding intermediate?

et al. 2009

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Influence of 12 nonpolar amino acids residues from the hydrophobic core of apomyoglobin on stability of its native state and folding intermediate was studied. Six of the selected residues are from the A, G and H helices; these are conserved in structure of the globin family, although nonfunctional, that is, not involved in heme binding. The rest are nonconserved hydrophobic residues that belong to the B, C, D, and E helices. Each residue was substituted by alanine, and equilibrium pH-induced transitions in apomyoglobin and its mutants were studied by circular dichroism and fluorescent spectroscopy. The obtained results allowed estimating changes in their free energy during formation of the intermediate state. It was first shown that the strength of side chain interactions in the apomyoglobin intermediate state amounts to 15-50% of that in its native state for conserved residues, and practically to 0% for nonconserved residues. These results allow a better understanding of interactions occurring in the intermediate state and shed light on involvement of certain residues in protein folding at different stages.

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Thermodynamic Puzzle of Apomyoglobin Unfolding

Cited by 143 publications

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Acid induced equilibrium unfolding of annexin V wild type shows two intermediate states

Acid induced equilibrium unfolding of annexin V wild type shows two intermediate states

Effects of pressure on the structure of metmyoglobin: Molecular dynamics predictions for pressure unfolding through a molten globule intermediate

How strong are side chain interactions in the folding intermediate?

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