Compatibility of osmolytes with Gibbs energy of stabilization of proteins

Anjum, Farah; Rishi, Vikas; Ahmad, Faizan

doi:10.1016/s0167-4838(99)00215-0

Cited by 102 publications

(69 citation statements)

References 33 publications

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“…The temperature dependence of osmolyte-induced stabilization is also not well characterized. Recent data (55) suggest that stabilization only occurs at higher temperatures and not at room temperature, although large extrapolations of measured T m values were involved in arriving at this conclusion. This observation is hard to explain on the basis of model compound ⌬G 0 tr studies.…”

Section: Discussionmentioning

confidence: 99%

Osmolytes Stabilize Ribonuclease S by Stabilizing Its Fragments S Protein and S Peptide to Compact Folding-competent States

Ratnaparkhi¹,

Varadarajan²

2001

Journal of Biological Chemistry

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Osmolytes stabilize proteins to thermal and chemical denaturation. We have studied the effects of the osmolytes sarcosine, betaine, trimethylamine-N-oxide, and taurine on the structure and stability of the protein⅐peptide complex RNase S using x-ray crystallography and titration calorimetry, respectively. The largest degree of stabilization is achieved with 6 M sarcosine, which increases the denaturation temperatures of RNase S and S pro by 24.6 and 17.4°C, respectively, at pH 5 and protects both proteins against tryptic cleavage. Four crystal structures of RNase S in the presence of different osmolytes do not offer any evidence for osmolyte binding to the folded state of the protein or any perturbation in the water structure surrounding the protein. The degree of stabilization in 6 M sarcosine increases with temperature, ranging from ؊0.52 kcal mol ؊1 at 20°C to ؊5.4 kcal mol ؊1 at 60°C. The data support the thesis that osmolytes that stabilize proteins, do so by perturbing unfolded states, which change conformation to a compact, folding competent state in the presence of osmolyte. The increased stabilization thus results from a decrease in conformational entropy of the unfolded state.Osmolytes are molecules used in nature to protect organisms against stresses of high osmotic pressure. These compounds have also been found to stabilize the native state of proteins relative to the unfolded state. The mechanism of this stabilization is not completely understood (1-4), although it is believed to result primarily from an unfavorable free energy of interaction between the osmolyte and the unfolded state of the protein (5, 6). Proteins retain activity in the presence of osmolytes suggesting that native state structure and dynamics are not greatly perturbed. However, there is little high resolution structural information available for proteins in the presence of osmolytes. The main classes of osmolytes are sugars, methyl ammonium derivatives, polyhydric alcohols, and amino acids and their derivatives (1). Molar concentrations of all the above classes of molecules have been shown to stabilize proteins. Many organisms accumulate osmolytes under conditions of water stress, such as high salinity, desiccation or freezing. In vivo, amino acid derivatives also counteract the accumulation of urea, which is capable of denaturing proteins. Marine cartilaginous fishes use, as osmolytes, a combination of urea and methylamines, i.e. a denaturant and a stabilizer, in a 2:1 ratio (1,7,8). Stability studies on RNase T1, RNase A, and other proteins have shown that, if the 2:1 ratio of urea:methylamine is maintained, the methylamine is able to counteract the destabilizing effect of the denaturant (1,7,8).In an effort to further our understanding of the basis of osmolyte stabilization of proteins, we have studied the stabilization of the fragment complementation system ribonuclease S (RNase S) 1 in four structurally similar osmolytes, namely sarcosine, betaine, trimethylamine-N-oxide (TMAO), and taurine. RNase S is a complex of two fragm...

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Section: Discussionmentioning

confidence: 99%

Osmolytes Stabilize Ribonuclease S by Stabilizing Its Fragments S Protein and S Peptide to Compact Folding-competent States

Ratnaparkhi¹,

Varadarajan²

2001

Journal of Biological Chemistry

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“…According to Shtereva et al, (2008), PEG induced drought stress increases endogenous proline concentration in tomato. According to Anjum et al, (2000), proline is a scavenger of OH * radical and plays an important role in osmotic adjustment during oxidative stress. It reduces the damaging effect of ROS to the membrane lipid and protein, enzymes and DNA.…”

Section: Impact Of Ppfm and Pgrs On Prolinementioning

confidence: 99%

Impact of Pink Pigmented Facultative Methylotroph and PGRs on Water Status, Photosynthesis, Proline and NR Activity in Tomato under Drought

Sivakumar¹,

Nandhitha²,

Chandrasekaran³

et al. 2017

Int.J.Curr.Microbiol.App.Sci

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“…Since the protection provided by an osmolyte does not depend on specific chemical interactions with the macromolecules, in principle, any of the osmolytes should be capable of replacing each other, depending upon either endogenous or exogenous availability of particular osmolyte(s) [94]. Since the role of protein backbone is critical in determining thermodynamic stability and folding of proteins in osmolyte solutions [95][96][97][98][99], designing these small molecules (osmolytes) appears to be an excellent strategy and could be a critical step in preventing various critical proteins from misfolding or aggregating [6]. This may have far reaching consequences in understanding and preventing several deleterious diseases that are caused by protein misfolding/aggregation [100,101].…”

Section: Preventing Aggregation and Oligmoerization Of Amyloid-β Withmentioning

confidence: 99%

Protective Role of Methylene Blue in Alzheimer's Disease via Mitochondria and Cytochrome c Oxidase

Atamna

Kumar

2010

JAD

120

100

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Abstract. The key cytopathologies in the brains of Alzheimer's disease (AD) patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of toxic species of amyloid-β (Aβ) peptides. This review discusses two potential approaches to delay the onset of AD. The first approach is use of diaminophenothiazines (e.g., methylene blue; MB) to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. We have shown that MB increases heme synthesis, cytochrome c oxidase (complex IV), and mitochondrial respiration, which are impaired in AD brains. Consistently, MB is one of the most effective agents to delay senescence in normal human cells. A key action of MB appears to be enhancing mitochondrial function, which is achieved at nM concentrations. We propose that the cycling of MB between the reduced leucomethylene blue (MBH2) and the oxidized (MB) forms may explain, in part, the mitochondria-protecting activities of MB. The second approach is use of naturally occurring osmolytes to prevent the formation of toxic forms of Aβ. Osmolytes (e.g., taurine, carnosine) are brain metabolites typically accumulated in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation, without perturbing other cellular processes. Experimental evidence suggests that the level of carnosine is significantly lower in AD patients. Osmolytes may inhibit the formation of Aβ species in vivo, thus preventing the formation of soluble oligomers. Osmolytes are efficient antioxidants that may also increase neural resistance to Aβ. The potential significance of combining MB and osmolytes to treat AD are discussed.

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Compatibility of osmolytes with Gibbs energy of stabilization of proteins

Cited by 102 publications

References 33 publications

Osmolytes Stabilize Ribonuclease S by Stabilizing Its Fragments S Protein and S Peptide to Compact Folding-competent States

Osmolytes Stabilize Ribonuclease S by Stabilizing Its Fragments S Protein and S Peptide to Compact Folding-competent States

Impact of Pink Pigmented Facultative Methylotroph and PGRs on Water Status, Photosynthesis, Proline and NR Activity in Tomato under Drought

Protective Role of Methylene Blue in Alzheimer's Disease via Mitochondria and Cytochrome c Oxidase

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