Biomedical subjects

Chad D Tatko

Publications and source records attributed to Chad D Tatko.

7 recordsLinked to original sources

PubMed2006

Polar networks control oligomeric assembly in membranes.

Polar interactions have a profound influence on membrane stability and structure. A membrane-solubilized GCN4 peptide, MS-1, is used to study the impact of polar networks. Amide functionalities from amino acid side chains have been shown to promote peptide oligomerization, but lacked specificity. Herein, the hydrogen bonding interactions of an Asn side chain are coupled with the hydroxyl of Ser or Thr to generate a polar network. Analytical ultracentrifugation and fluorescence resonance energy transfer studies indicate that a trimer assembly is established where each membrane-embedded hydrogen bond contributes 1 kcal mol-1.

Amino Acid Sequence↗

PubMed2004

Effect of halogenation on edge-face aromatic interactions in a beta-hairpin peptide: enhanced affinity with iodo-substituents.

[reaction: see text] In a model beta-hairpin peptide, we have found that the favorable interaction of cross-strand aromatic rings can be enhanced by up to 1 kcal mol(-1) with halogen substituents. It appears that the polarizability of the halogen atoms accounts for the increase in stability and that there is a direct interaction between the N-terminal phenylalanine and the halogen atom. Thermal denaturation studies indicate that the interaction is enthalpically driven with an associated entropic cost. These findings have relevance to areas of molecular recognition and drug design.

Amino Acid Sequence↗

PubMed2004

Comparison of C-H...pi and hydrophobic interactions in a beta-hairpin peptide: impact on stability and specificity.

We have examined the impact of C-H...pi and hydrophobic interactions in the diagonal position of a beta-hairpin peptide through comparison of the interaction of Phe, Trp, or Cha (cyclohexylalanine) with Lys or Nle (norleucine). NMR studies, including NOESY and chemical shift perturbation studies, of the Lys side chain indicates that Lys interacts in a specific geometry with Phe or Trp through the polarized C epsilon. In contrast, Nle does not interact in a specific manner with the diagonal aromatic residue. Thermal denaturation provides additional support that Lys and Nle interact in fundamentally different manners. Folding of the peptide with a diagonal Trp...Lys interaction was found to be enthalpically driven, whereas the peptide with a diagonal Trp...Nle interaction displayed cold denaturation, as did the control peptide with a diagonal Cha...Nle interaction, indicating different driving forces for interaction of Lys and Nle with Trp. These findings have significant implications for specificity in protein folding and de novo protein design.

Anisotropy↗

PubMed2004

Investigation of the nature of the methionine-pi interaction in beta-hairpin peptide model systems.

There are frequent contacts between aromatic rings and sulfur atoms in proteins. However, it is unclear to what degree this putative interaction is stabilizing and what the nature of the interaction is. We have investigated the aryl-sulfur interaction by placing a methionine residue diagonal to an aromatic ring on the same face of a beta-hairpin, which places the methionine side chain in close proximity to the aryl side chain. The methionine (Met)-aryl interaction was compared with an equivalent hydrophobic and cation-pi interaction in the context of the beta-hairpin. The interaction between phenylalanine (Phe), tryptophan (Trp), or cyclohexylalanine (Cha) and Met stabilized the beta-hairpin by -0.3 to -0.5 kcal mole(-1), as determined by double-mutant cycles. The peptides were subjected to thermal denaturations that suggest a hydrophobic driving force for the interactions between Met and Trp or Cha. The observed interaction of Met or norleucine (Nle) with Trp or Cha are quite similar, implying a hydrophobic driving force for the Met-pi interaction. However, the thermodynamic data suggest that there may be some differences between the interaction of Met with Trp and Phe and that there may be a small thermodynamic component to the Met...Phe interaction.

Amides↗

PubMed2003

The geometry and efficacy of cation-pi interactions in a diagonal position of a designed beta-hairpin.

Cation-pi interactions are common in proteins, but their contribution to the stability and specificity of protein structure has not been well established. In this study, we examined the impact of cation-pi interactions in a diagonal position of a beta-hairpin peptide through comparison of the interaction of Phe or Trp with Lys or Arg. The diagonal interactions ranged from -0.20 to -0.48 kcal/mole. Our experimental values for the diagonal cation-pi interactions are similar to those found in alpha-helical studies. Upfield shifting of the Lys and Arg side chains indicates that the geometries of cation-pi interactions adopted in the 12-residue beta-hairpin are comparable to those found in protein structures. The Lys was found to interact through the polarized Cepsilon, and the Arg is stacked against the aromatic ring of Phe or Trp. Folding of these peptides was found to be enthalpically favorable (DeltaH degrees equals approximately -3 kcal/mole) and entropically unfavorable (DeltaS degrees equals approximately -8 cal mole(-1) K(-1)).

Arginine↗

PubMed2002

Simple cation-pi interaction between a phenyl ring and a protonated amine stabilizes an alpha-helix in water.

Cation-pi interactions have been proposed to be important contributors to protein structure and function. In particular, these interactions have been suggested to provide significant stability at the solvent-exposed surface of a protein. We have investigated the magnitude of cation-pi interactions between phenylalanine (Phe) and lysine (Lys), ornithine (Orn), and diaminobutanoic acid (Dab) in the context of an alpha-helix and have found that only the Phe...Orn interaction provides significant stability to the helix, stabilizing it by -0.4 kcal/mol. This interaction energy is in the same range as a salt bridge in an alpha-helix, and equivalent to the recently reported Trp...Arg interaction in an alpha-helix, despite the fact that Trp...guanidinium interactions have been proposed to be stronger than Phe...ammonium interactions. These results indicate that even the simplest cation-pi interaction can provide significant stability to protein structure and demonstrate the subtle factors that can influence the observed interaction energies in designed systems.

Amino Acid Sequence↗

PubMed2002

Selective aromatic interactions in beta-hairpin peptides.

To probe the selectivity possible in hydrophobic clusters, we have compared the cross-strand interactions of phenylalanine (Phe) and cyclohexylalanine (Cha) in a beta-hairpin peptide. We have found a preference for self-association among the aromatic residues, which provides 0.55 kcal/mol in stability relative to Cha-Cha cross-strand pair. NMR analysis of the Phe-Phe cross-strand pair indicates that it interacts in an edge-face interaction, despite the fact that it is highly solvent-exposed. The interaction geometry as well as the enthalpic and entropic values for the peptide containing the Phe-Phe cross-strand pair suggest that the preference for self-association arises from inherent differences in the nature of aromatic and aliphatic interactions in water.

Peptides↗