Stability of an amide-hydrogen bond in an apolar environment

Klotz, Irving M.; Farnham, Sutton B.

doi:10.1021/bi00851a013

Cited by 68 publications

(43 citation statements)

References 6 publications

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“…This point becomes clear upon examination of the data in Table 1, when it is realized that most of the free energies of transfer from water to the condensed vapor are actually unfavorable, many by a considerable amount. This is due, of course, to the fact that water participates in strong interactions with hydrogenbond donors and acceptors (Klotz & Farnham, 1968), as well as to the need to neutralize charged side-chains. As a result, one of the major free energy deficits in the folding of a protein results from the requirement to unsolvate those hydrophilic functional groups destined for the interior.…”

Section: Discussionmentioning

confidence: 99%

A simple method for displaying the hydropathic character of a protein

Kyte

Doolittle

1982

Journal of Molecular Biology

21,313

256

12,351

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Section: Discussionmentioning

confidence: 99%

A simple method for displaying the hydropathic character of a protein

Kyte

Doolittle

1982

Journal of Molecular Biology

21,313

256

12,351

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“…peptide groups are hydrogen bonded to water molecules in the solvent or to each other in the interior of the native protein (31,33).…”

Section: Discussionmentioning

confidence: 99%

Thermodynamics of the self-association of glucagon.

Formisano¹,

Johnson²,

Edelhoch³

1977

Proc. Natl. Acad. Sci. U.S.A.

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In water, glucagon exists in an equilibrium between a trimer in which more tan half of the peptide groups are in an a-helical configuration and a monomer which has a random coil configuration with few a-helical residues. The thermodynamics of this self-association have been evaluated by studying the temperature-and concentration-dependence of the mean residue ellipticity at 220 nm. The enthalpy and entropy changes of association were negative at all temperatures between 50 and 500 and had large negative temperature dependencies. Usually an association that involves nonpolar groups is considered to be driven by a positive entropy term. Such an explanation is not tenable in the case of glucagon. However, i the effects of nonpolar groups on the coil-to-helix transition of a p tide areincluded into the thermodynamic considerations ofhydrophobic interactions, then the negative parameters observed for glucagon association can be readily understood. The hydrophobic interaction is therefore not necessarily controlled by the entropy change because, if there are significant conformational changes, the reaction may be controlled by the enthalpy change. Consequently, the more important parameter characteristic of all hydrophobic reactions is the heat capacity change.Glucagon is a 29-residue polypeptide hormone that is bound to target tissues and activates adenyl cyclase. Treatment of liver plasma membranes with reagents that modify membrane structure (i.e:, digitonin or phospholipase A) inhibits both glucagon binding and stimulation of adenylate cyclase activity (1). It has been suggested from studies of the binding of glucagon fragments that the hydrophobic region at the carboxyl end of the molecule is important for binding and activation of adenylate cyclase (2). Recent x-ray diffraction studies of glucagon crystals revealed the formation of a trimer with very strong hydrophobic interactions between the glucagon chains which are largely a-helical (3). In order to understand these interactions, which may play an important role in glucagon binding to its membrane receptor (4) A recent conformational analysis based on the sequence of glucagon suggests that glucagon can readily fold into different conformations (5). In very dilute solutions, glucagon is largely unfolded with'few stable intramolecular bonds (6-9). With increasing concentration, in dilute alkali glucagon forms timers that are highly a-helical and in acid it forms fibrils whose folding is mainly of ,8-structure (6). In certain organic solvents (ethylene or propylene glycol/water mixtures), glucagon folds into a a-helical structure but does not associate (10). Glucagon also becomes more a-helical when bound to lipids-i.e., cationic detergents (11), phospholipid micelles (12), or bilayers (13).We have evaluated the thermodynamic parameters of glucagon association between 50 and 500. These should be of interest in understanding not only the interactions between glucagon molecules but also other reactions that depend on hydrophobic forces. Typical examples ...

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“…Based on model compound data, it was not clear whether the free energy change for this reaction was favorable or unfavorable. For example, Klotz suggested −750 cal mol −1 and Schellman suggested + 400 cal mol −1 as the free energy change for this reaction. In Kauzmann's important 1959 review, he made a strong case for the importance of hydrophobic bonds but concluded: “··· it is likely that hydrogen bonds between peptide links and hydrophobic bonds are by far the most important in determining the over‐all configuration of the protein molecule.…”

Section: Introductionmentioning

confidence: 99%

Contribution of hydrogen bonds to protein stability

et al. 2014

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Our goal was to gain a better understanding of the contribution of the burial of polar groups and their hydrogen bonds to the conformational stability of proteins. We measured the change in stability, D(DG), for a series of hydrogen bonding mutants in four proteins: villin headpiece subdomain (VHP) containing 36 residues, a surface protein from Borrelia burgdorferi (VlsE) containing 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa (RNase Sa) and T1 (RNase T1). Crystal structures were determined for three of the hydrogen bonding mutants of RNase Sa: S24A, Y51F, and T95A. The structures are very similar to wild type RNase Sa and the hydrogen bonding partners form intermolecular hydrogen bonds to water in all three mutants. We compare our results with previous studies of similar mutants in other proteins and reach the following conclusions. (1) Hydrogen bonds contribute favorably to protein stability. (2) The contribution of hydrogen bonds to protein stability is strongly context dependent. (3) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. (4) Polar group burial can make a favorable contribution to protein stability even if the polar groups are not hydrogen bonded. (5) The contribution of hydrogen bonds to protein stability is similar for VHP, a small protein, and VlsE, a large protein.

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Stability of an amide-hydrogen bond in an apolar environment

Cited by 68 publications

References 6 publications

A simple method for displaying the hydropathic character of a protein

A simple method for displaying the hydropathic character of a protein

Thermodynamics of the self-association of glucagon.

Contribution of hydrogen bonds to protein stability

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