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Side-chain Interactions (side-chain + interaction)
Selected Abstracts,-Hairpin folding and stability: molecular dynamics simulations of designed peptides in aqueous solutionJOURNAL OF PEPTIDE SCIENCE, Issue 9 2004Clara M. Santiveri Abstract The structural properties of a 10-residue and a 15-residue peptide in aqueous solution were investigated by molecular dynamics simulation. The two designed peptides, SYINSDGTWT and SESYINSDGTWTVTE, had been studied previously by NMR at 278 K and the resulting model structures were classified as 3:5 ,-hairpins with a type I + G1 ,-bulge turn. In simulations at 278 K, starting from the NMR model structure, the 3:5 ,-hairpin conformers proved to be stable over the time period evaluated (30 ns). Starting from an extended conformation, simulations of the decapeptide at 278 K, 323 K and 353 K were also performed to study folding. Over the relatively short time scales explored (30 ns at 278 K and 323 K, 56 ns at 353 K), folding to the 3:5 ,-hairpin could only be observed at 353 K. At this temperature, the collapse to ,-hairpin-like conformations is very fast. The conformational space accessible to the peptide is entirely dominated by loop structures with different degrees of ,-hairpin character. The transitions between different types of ordered loops and ,-hairpins occur through two unstructured loop conformations stabilized by a single side-chain interaction between Tyr2 and Trp9, which facilitates the changes of the hydrogen-bond register. In agreement with previous experimental results, ,-hairpin formation is initially driven by the bending propensity of the turn segment. Nevertheless, the fine organization of the turn region appears to be a late event in the folding process. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] New structural insights from Raman spectroscopy of proteins and their assembliesBIOPOLYMERS, Issue 4-5 2002George J. Thomas Jr.Article first published online: 9 MAY 200 Abstract Protein structure and stability are sensitive to and dependent on the local interactions of amino acid side chains. A diverse and important type of side-chain interaction is the hydrogen bond. Although numerous hydrogen bonds are resolved in protein 3-dimensional structures, those of the cysteine sulfhydryl group (S H) are elusive to high-resolution X-ray and NMR methods. However, the nature and strength of sulfhydryl hydrogen bonds (SH,X) are amenable to investigation by Raman spectroscopy. The power of the Raman method for characterizing SH,X interactions is illustrated by resolving the Raman SH stretching band for each of the eight cysteines per 666-residue subunit in the trimeric tailspike of icosahedral bacteriophage P22. The Raman sulfhydryl signatures of the wild-type tailspike and eight single-site cysteine to serine mutants reveal a heretofore unrecognized diversity of SH hydrogen bonds in a native protein. The use of Raman spectroscopy to identify the non-hydrogen-bonded state of the tyrosine phenoxyl group is also described. This unusual and unexpected state occurs for all tyrosines in the assembled capsids of filamentous viruses Ff and Pf1. The Raman spectral signature of the non-hydrogen-bonded tyrosine phenoxyl, which is characterized by an extraordinary Raman Fermi doublet intensity ratio (I850/I830 = 6.7), extends and refines the existing correlation for hydrogen-bonded tyrosines. Finally, a novel Raman signature for tryptophan in the Pf3 filamentous virus is identified, which is proposed as diagnostic of "cation,, interaction" involving the guanidinium group of Arg 37 as a cation donor and the indolyl ring of Trp 38 as a ,-electron acceptor. These studies demonstrate the power of Raman spectroscopy for investigating the interactions of key side chains in native protein assemblies. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 214,225, 2002 [source] Applications of model ,-hairpin peptidesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2004Carol E. Stotz Abstract In recent years, ,-hairpin peptides have been studied in great detail. Much of the focus has been on the thermodynamic stability of ,-hairpin structure. Structural measurements have been conducted with nuclear magnetic resonance, with additional information obtained from circular dichroism, Fourier transform infrared, and molecular dynamic simulation studies. Point mutations, both in the ,-strands and in the turn region, have systematically explored the role of turn sequence, side-chain,side-chain interactions, intramolecular hydrogen bonding, and ,-strand length on ,-hairpin peptide conformational stability. In addition to studying the elements of structural stability independently, the cooperative nature of the individual components to combine to form the overall structure has also been investigated. Because the ,-hairpin peptides often spontaneously form their conformation, they have begun to serve as models for studying peptide binding and therapeutic agents. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2881,2894, 2004 [source] Interdomain side-chain interactions in human ,D crystallin influencing folding and stabilityPROTEIN SCIENCE, Issue 8 2005Shannon L. Flaugh Abstract Human ,D crystallin (H,D-Crys) is a two domain, ,-sheet eye lens protein that must remain soluble throughout life for lens transparency. Single amino acid substitutions of H,D-Crys are associated with juvenile-onset cataracts. Features of the interface between the two domains conserved among ,-crystallins are a central six-residue hydrophobic cluster, and two pairs of interacting residues flanking the cluster. In H,D-Crys these pairs are Gln54/Gln143 and Arg79/Met147. We previously reported contributions of the hydrophobic cluster residues to protein stability. In this study alanine substitutions of the flanking residue pairs were constructed and analyzed. Equilibrium unfolding/refolding experiments at 37°C revealed a plateau in the unfolding/refolding transitions, suggesting population of a partially folded intermediate with a folded C-terminal domain (C-td) and unfolded N-terminal domain (N-td). The N-td was destabilized by substituting residues from both domains. In contrast, the C-td was not significantly affected by substitutions of either domain. Refolding rates of the N-td were significantly decreased for mutants of either domain. In contrast, refolding rates of the C-td were similar to wild type for mutants of either domain. Therefore, domain interface residues of the folded C-td probably nucleate refolding of the N-td. We suggest that these residues stabilize the native state by shielding the central hydrophobic cluster from solvent. Glutamine and methionine side chains are among the residues covalently damaged in aged and cataractous lenses. Such damage may generate partially unfolded, aggregation- prone conformations of H,D-Crys that could be significant in cataract. [source] Sequence dependence of ,-hairpin structure: Comparison of a salt bridge and an aromatic interactionPROTEIN SCIENCE, Issue 12 2003Sarah E. Kiehna Abstract A comparison of the contributions and position dependence of cross-strand electrostatic and aromatic side-chain interactions to ,-sheet stability has been performed by using nuclear magnetic resonance in a well-folded ,-hairpin peptide of the general sequence XRTVXVdPGOXITQX. Phe,Phe and Glu,Lys pairs were varied at the internal and terminal non,hydrogen-bonded position, and the resulting stability was measured by the effects on ,-hydrogen and aromatic hydrogen chemical shifts. It was determined that the introduction of a Phe,Phe pair resulted in a more folded peptide, regardless of position, and a more tightly folded core. Substitution of the Glu,Lys pair at the internal position results in a less folded peptide and increased fraying at the terminal residues. Upfield shifting of the aromatic hydrogens provided evidence for an edge-face aromatic interaction, regardless of position of the Phe,Phe pair. In peptides with two Phe,Phe pairs, substitution with Glu,Lys at either position resulted in a weakening of the aromatic interaction and a subsequent decrease in peptide stability. Thermal denaturation of the peptides containing Phe,Phe indicates that the aromatic interaction is enthalpically favored, whereas the folding of hairpins with cross-strand Glu,Lys pairs was less enthalpically favorable but entropically more favorable. [source] Hyperstability and crystal structure of cytochrome c555 from hyperthermophilic Aquifex aeolicusACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2009Marii Obuchi In order to elucidate the relationship between the stability and the structure of the monohaem cytochrome c555 (AA c555) from the hyperthermophilic bacterium Aquifex aeolicus, chemical denaturation and crystal structure determination were carried out. AA c555 exhibited higher stability than the thermophilic Hydrogenobacter thermophilus cytochrome c552 (HT c552), which is one of the most stable cytochromes c. The three-dimensional crystal structure of AA c555, which was determined using the multiple anomalous dispersion technique at 1.15,Å resolution, included a unique 14-residue extra helix, while the side-chain interactions of several amino-acid residues responsible for the stability of HT c552 were conserved in AA c555. The side chain of the Met61 residue in the extra helix was aligned towards the haem, forming a coordination bond between the Met S and haem Fe atoms. In other cytochromes c the corresponding regions always form , loops which also include the haem-liganding Met residue and are known to be involved in the initial step in cytochrome c denaturation. The formation of the extra helix in AA c555 results in the highest helix content, 59.8%, among the monohaem cytochromes c. The extra helix should mainly contribute to the hyperstability of AA c555 and is presumed to be a novel strategy of cytochromes c for adaptation to a hyperthermophilic environment. [source] Folding Dynamics of 10-Residue ,-Hairpin Peptide ChignolinCHEMISTRY - AN ASIAN JOURNAL, Issue 5 2007Atsushi Suenaga Dr. Abstract Short peptides that fold into ,-hairpins are ideal model systems for investigating the mechanism of protein folding because their folding process shows dynamics typical of proteins. We performed folding, unfolding, and refolding molecular dynamics simulations (total of 2.7,,s) of the 10-residue ,-hairpin peptide chignolin, which is the smallest ,-hairpin structure known to be stable in solution. Our results revealed the folding mechanism of chignolin, which comprises three steps. First, the folding begins with hydrophobic assembly. It brings the main chain together; subsequently, a nascent turn structure is formed. The second step is the conversion of the nascent turn into a tight turn structure along with interconversion of the hydrophobic packing and interstrand hydrogen bonds. Finally, the formation of the hydrogen-bond network and the complete hydrophobic core as well as the arrangement of side-chain,side-chain interactions occur at approximately the same time. This three-step mechanism appropriately interprets the folding process as involving a combination of previous inconsistent explanations of the folding mechanism of the ,-hairpin, that the first event of the folding is formation of hydrogen bonds and the second is that of the hydrophobic core, or vice versa. [source] | ||||||||||