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The investigation of the structural properties of hematopoietic cytokines, human prolactin (hPRL) reported unexpected pH dependence to its stability over the physiologic range of approximately 6.0-8.0. Results show that surface plasmon resonance analysis of the interaction between hPRL and the extracellular domain (ECD) of the hPRL receptor brings out a selective 500-fold change in the dissociation rate between pH 8.3 and pH 5.8.

NMR spectroscopy is used to describe the consequences of binding sinefungin, a S-adenosylmethionine (SAM) analogue, on the structure and dynamics of the thiopurine methyltransferase (TPMT) protein backbone. The potential implications for the structural and dynamic effects of binding sinefungin for the catalytic mechanism of the enzyme and the stabilization of the degradation-susceptible TPMT polymorphs are discussed.

The folding of intestinal fatty acid binding protein is described. This protein contains two beta sheets and a small helical domain that surrounds a large ligand-binding cavity in the interior of the protein.

Amide 15N relaxation and 1H exchange nuclear magnetic resonance spectroscopy were done to elucidate the dynamics of the liganded (holo) and unliganded (apo) forms of rat intestinal fatty acid-binding protein (I-FABP) derived from Escherichia coli. The results indicated that the bound fatty acid engages in a series of long-range cooperative interactions that cap and stabilize the C-terminal half of helix II, leading to an ordering of the portal region. Such observations provide evidence that I-FABP affect the ligand-regulated order-disorder transition which occur during fatty acid transport and targeting.

The three-dimensional structure of the unliganded form of Escherichia coli-derived rat intestinal fatty acid-binding protein (I-FABP) was determined by triple-resonance three-dimensional nuclear magnetic resonance techniques. Findings indicated that the structural variability was indicative of backbone disorder in apo-I-FABP. The disorder was greatest in residues K29-L36 and N54-N57, encompassing the distal half of alpha-helix II, the linker between helix II and beta-strand B, and the reverse turn between beta-strands C and D.

NMR spectroscopy was used to monitor site-specific proton binding to eight of nine histidine residues from human prolactin (hPRL) and derive their equilibrium dissociation constants. The findings from complex protonation reactions provide insight into the biophysical mechanism of pH-dependent regulation of hPRL's structural and functional properties.

The solution structure of a beta-peptide foldamer in methanol is described. The structure reveals the details of a helix-stabilizing salt bridge on one helical face, novel 'wedge into cleft' packing along another, and distortions in the beta-peptide foldamer 14-helix that may maximize presentation of the p53 activation domain recognition epitope.

A set of four beta(super 3)-peptides (betaWWW-1-4) is synthesized containing WW1epitope in both possible orientations on each available face of a beta(super 3)-decapeptide possessing significant 14-helix stability in aqueous solution due to electrostatic macrodipole stabilization and side chain-side chain salt bridges. The results show that molecules such as beta(super 3) peptides betaWW-1-4 could represent leads towards inhibitors or antigens effective against HIV or other viruses, such as SARS(super 30), Ebola, HRSV, and influenza that employ common fusion mechanisms.

The article presents a solution structure of a β-peptide ligand for hDM2. A β-peptide foldamer, β-1 is analyzed that assembles into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). The solution structure of β-1 in methanol is presented. The structure reveals details of a helix-stabilizing salt bridge on one helical face, novel "wedge into cleft" packing along another, and distortions in the β-1, 14-helix that may maximize presentation of the p53AD recognition epitope.

This article focuses on a study related to helical β-peptide inhibitors of the p53-hDM2 interaction. β-Peptides differ from α-peptides by one additional backbone carbon atom and by resistance to metabolism and proteolysis.β-Peptides fold into helices, sheets, and turns and have well-recognized potential as peptidomimetics. hDM2 is recognized in vivo by a short α-helix within the activation domain of p53, the transcription factor that controls cell fate in response to stress.

The article reports on inhibiting HIV fusion with a β-peptide foldamer. Linear peptides derived from the HIV gp4 1 C-terminus (C-peptides), such as the 36-residue Fuzeon, are potent HIV fusion inhibitors. These molecules bind to the N-peptide region of gp4 1 and act as dominant negative inhibitors of an intramolecular protein-protein interaction that powers fusion of the viral and host cell membranes. The gp4l N-peptide region contains a surface pocket that is less prone to mutation than other gp4 1 regions or HIV enzymes.