Tyrosine hydrogen bonds make a large contribution to protein stability

Pace, C. Nick; Horn, G.; Hebert, Eric; Bechert, J.; Shaw, Kevin L.; Urbanikova, L.; Scholtz, J. Martin; Ševčı́k, Jozef

doi:10.1006/jmbi.2001.4956

Cited by 132 publications

(140 citation statements)

References 72 publications

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“…Thermal Denaturation-The thermal denaturation of RNase Sa and all of the single mutants studied to date is reversible and closely approaches a two-state folding mechanism (15,26,28). Thermal denaturation curves were determined and analyzed as described above, and the results are presented in Table II.…”

Section: Resultsmentioning

confidence: 99%

“…In summary, these results suggest that a polar -OH group may make a larger contribution to the stability of a protein than a nonpolar -CH 3 group even when the -OH group is not hydrogen-bonded. We showed previously that the buried -OH groups of Tyr residues can make a favorable contribution to protein stability even when they are not hydrogen-bonded in the folded protein (15).…”

Section: Discussionmentioning

confidence: 99%

“…Proteins-RNase Sa and mutants thereof were prepared, expressed, and purified as previously described (15,33). The protein solutions were buffered at pH 7.0 with 30 mM MOPS.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies of hydrogen bonding used mutants such as Tyr-to-Phe mutants in which a hydrogen-bonded group was removed and a cavity may be created (15). A different approach is to use Thr-to-Val and Val-to-Thr mutations with the -OH group of a Thr or the -CH 3 group of a Val interchanged.…”

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confidence: 99%

“…We have previously compared the stability of RNase Sa and two close relatives, RNase Sa2 and RNase Sa3, and determined the pH and salt dependence of their stability (25). We have shown that a conserved Asn residue (26) and the Tyr -OH groups (15) make large contributions to the stability of RNase Sa. We have studied the contribution of charge-charge interactions to the stability of RNase Sa (27).…”

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confidence: 99%

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The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent

Takano

Scholtz

Sacchettini

et al. 2003

Journal of Biological Chemistry

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We previously suggested that proteins gain more stability from the burial and hydrogen bonding of polar groups than from the burial of nonpolar groups (Pace, C. N. (2001) Biochemistry 40, 310 -313). To study this further, we prepared eight Thr-to-Val mutants of RNase Sa, four in which the Thr side chain is hydrogen-bonded and four in which it is not. We measured the stability of these mutants by analyzing their thermal denaturation curves. The four hydrogen-bonded Thr side chains contribute 1.3 ؎ 0.9 kcal/mol to the stability; those that are not still contribute 0.4 ؎ 0.9 kcal/mol to the stability. For 40 Thr-to-Val mutants of 11 proteins, the average decrease in stability is 1.0 ؎ 1.0 kcal/mol when the Thr side chain is hydrogen-bonded and 0.0 ؎ 0.5 kcal/mol when it is not. This is clear evidence that hydrogen bonds contribute favorably to protein stability. In addition, we prepared four Val-to-Thr mutants of RNase Sa, measured their stability, and determined their crystal structures. In all cases, the mutants are less stable than the wild-type protein, with the decreases in stability ranging from 0.5 to 4.4 kcal/mol. For 41 Val-to-Thr mutants of 11 proteins, the average decrease in stability is 1.8 ؎ 1.3 kcal/mol and is unfavorable for 40 of 41 mutants. This shows that placing an -OH group at a site designed for a -CH 3 group is very unfavorable. So, -OH groups can contribute favorably to protein stability, even if they are not hydrogen-bonded, if the site was selected for an -OH group, but they will make an unfavorable contribution to stability, even if they are hydrogen-bonded, when they are placed at a site selected for a -CH 3 group. The contribution that polar groups make to protein stability depends strongly on their environment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Proteins-RNase Sa and mutants thereof were prepared, expressed, and purified as previously described (15,33). The protein solutions were buffered at pH 7.0 with 30 mM MOPS.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent

Takano

Scholtz

Sacchettini

et al. 2003

Journal of Biological Chemistry

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Pressure Sensitive Adhesion of an Elastomeric Protein Complex Extracted From Squid Ring Teeth

Pena‐Francesch

Akgün

Miserez

et al. 2014

Adv Funct Materials

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The pressure sensitive adhesion characteristic of a protein complex extracted from squid ring teeth (SRT), which exhibits an unusual and reversible transition from a solid to a melt, is studied. The native SRT is an elastomeric protein complex that has standard amino acids, and it does not function as adhesives in nature. The SRT can be thermally shaped into any 3D geometry (e.g., thin films, ribbons, colloids), and it has a glass transition temperature of 32 °C in water. Underwater adhesion strength of the protein film is approximately 1.5–2.5 MPa. The thermoplastic protein film could potentially be used in an array of fields, including dental resins, bandages for wound healing, and surgical sutures in the body.

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Hydrophobic tendencies of polar groups as a major force in molecular recognition

Chalikian

2003

Biopolymers

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Proteins and nucleic acids are able to adopt their native conformation and perform their biological role only in the presence of water with which they actively interact in a mutually modifying way. Traditionally, hydrophobic effect has been considered to be the major factor stabilizing biopolymeric structures. However, solvent reorganization around polar groups is an event thermodynamically more unfavorable than solvent reorganization around nonpolar groups. Consequently, burial of polar groups with formation of complementary solute-solute hydrogen bonds out of contact with water is an energetically favorable process that also provides a major force driving macromolecular association and folding. In contrast to nonpolar groups, polar groups may form their complementary intra- or intersolute hydrogen bonds out of contact with water only provided that an appropriate solute structure has been formed with properly positioned hydrogen bond donors and acceptors. Formation of such structures is disfavored entropically and may not be possible due to steric reasons. However, the interior of a folded protein, alpha-helices and beta-sheets, double helical nucleic acid structures, and protein-ligand interfaces all provide rigid matrices where polar groups may form their complementary hydrogen bonds. For these structures, the inward drive of polar groups represents a considerable stabilizing factor.

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Tyrosine hydrogen bonds make a large contribution to protein stability

Cited by 132 publications

References 72 publications

The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent

The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent

Pressure Sensitive Adhesion of an Elastomeric Protein Complex Extracted From Squid Ring Teeth

Hydrophobic tendencies of polar groups as a major force in molecular recognition

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