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The stability of cyclic beta-hairpins is examined. It is found that side-chain substitutions of hydrogen-bonded strand positions play an important role in its stability.

Research has been conducted on the insulin-like growth factor-1 protein. The crystallization of this protein in the presence of the detergent big CHAPS has been carried out and its structure has been determined via the multiwavelength anomalous diffraction.

Research has been conducted on the interactions between insulin-like growth factor 1(IGF-I) and IGF binding protein 1 (IGFBP-1). The turn-helix peptide motif necessary for the IGFBP-1 binding and structural integrity has been analyzed and described.

Research into the structural stability of 10-residue, disulfide-constrained beta-hairpins and their suitability as scaffolds for beta-turn display is presented. It was possible to produce a beta-turn scaffold that can be used to display peptide libraries of restricted conformational diversity on phage.

Author(s): Mark S. Dennis; Charles Eigenbrot; Nicholas J. Skelton; Mark H. Ultsch; Lydia Santell; Mary A. Dwyer [1]; Mark P. O'Connell; Robert A. Lazarus (corresponding author) Initiation of the extrinsic [...]

A study of the 32-kDa complex formed between an E-domain mutant and Fv-fragment of the humanized anti-HER2 antibody is presented. Results characterize the interface formed by SpA repeats.

New peptides that are not related to insulin-like growth factor 1 (IGF-1) but can bind with IGF-binding proteins (IGFBP) and can replace IGF-1 from IGFBP-1 complexes in vitro have been identified. One of the peptides has a well-developed turn-helix structure which can be used in synthesizing small molecule mimetics. The peptide also contains the IGF-1 region that is involved in IGFBP binding but has side chains that are unlike those of the IGF-1 helix I.

The implications for phosphorylation and molecular recognition of Bacillus subtilis response regulator (Spo0F) was investigated by employing high-resolution magnetic resonance structure. Results revealed the presence of relative charge distribution residues located at the site of phosphorylation. This is essential in providing specificity for protein-protein interactions and determining lifetimes of the phosphorylated state.

A procedure for constraining short peptides of arbitrary sequence to an alpha-helical conformation was developed. Glutamine residues at positions i and i+7 of the peptides were tethered with an alkanediyl chain between the side chain nitrogen atoms. Peptides having this tether were easily synthesized on the solid phase by amide formation between an alpha,omega-diaminoalkane and the side chain carboxylates of glutamate residues. The resulting cyclic peptides were observed to adopt an alpha-helical conformation in aqueous solution.

The solution structure of the uncomplexed E-domain were determined utilizing 2D homonuclear and heteronuclear NMR spectroscopy to investigate further the structural characteristics of Fc binding of staphylococcal protein A and as a first step in developing a structural understanding of E-domain/Fv complex formation. No significant differences in the overall structure result from various orientations of Phe11. The solution structure of the E-domain is composed of three alpha-helices that pack together to produce a compact helical bundle. A detailed comparison between the E-domain ensembles and the previously determined structure for the B-domain in complex with Fc indicates that only the 180 degrees chi-1 rotamer of Phe11 is competent for binding.

Nuclear magnetic resonance spectroscopic examination of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain showed a high degree of similarity to the human EGF, which differed only in the well-defined beta-strand of the N-terminal residues 2-6. This beta-strand defines the receptor specificity differences between HRG-alpha and human EGF.

RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), a protein from chemotactic cytokine family, is highly aggregated, up to >1.0 mM in solutions above pH 4.0. At pH 3.7 the protein is generally dimeric. Proton nuclear magnetic resonance (H NMR) was used to investigate RANTES' structural properties. The analysis of the sequential and medium range nuclear Overhauser effect and backbone scalar coupling constants show that RANTES contains a three stranded anti-parallel beta-sheet.

Analysis of the solution structure of peptide hormone guanylin by nuclear magnetic resonance reveals that the peptides, prepared by solid-phase chemical synthesis and from a 99 residue proprotein, consist of two isoforms that have different conformations and a 1:1 ratio. The first isoform structure is well defined and has a right-handed spiral conformation while the second isoform structure with a left-hand spiral conformation is not well defined. The structural variations indicate that the affinity of the two isoforms towards the STa receptor is distinct.

Bioactive linear peptidomimetics and cyclic peptides conformations in arginine-glycine-aspartic acid (RGD) sequence are identified with the help of an ensemble molecular dynamics method. Conformational transformations occur through various low energy pathways. Multiple simulations with different starting points increase the sampling efficiency. Non-peptidal inhibitors are designed with the help of this structural model.

15N nuclear magnetic resonance (NMR) spectroscopy is used to determine the properties of the backbone dynamics of apo-and (Cd2+)1-calbindin D9K. 15N-enriched samples are used in two-dimensional, proton-detected heteronuclear NMR studies to calculate the spin-lattice and spin-spin relaxation rate constants and steady-state {1H}-15N nuclear overhauser effects. A model-free formalism is used to study the relaxation parameters which help determine the properties of the dynamics of N-H bond vectors.

Research was conducted on the backbone dynamics of calbindin D9k loaded with calcium using two-dimensional proton-detected 15N nuclear magnetic resonance spectroscopy. Results revealed a similarity between the amplitude of motions for the calcium-binding loops and the helices. Three distinct categories were also determined for the correlation between the backbone order parameters and the amide hydrogen exchange rates of calcium-loaded calbindin D9k.