Protein and Peptide Letters - Volume 15, Issue 2, 2008

This issue of Protein and Peptide Letters (PPL) features two papers from the team of Alfredo Tomasselli and Bob Heinrikson and their colleagues [119-143]. Both of these contributions are slightly longer than typical PPL papers and both deal with the same enzyme, BACE, or β-secretase, a target for drug discovery for treatment of Alzheimer's Disease. What is the justification for taking up this much room in an issue of PPL? Read More

BACE, or β-secretase, is an attractive target in the treatment of Alzheimer's Disease because of its involvement in the generation of amyloid β peptides. BACE is a type I transmembrane aspartyl protease composed of pre-, pro-, catalytic, transmembrane and cytoplasmic domains. For the present study, the coding sequence was truncated just before the transmembrane domain and the resulting construct was extended wit Read More

BACE (β-site APP cleaving enzyme) or β-secretase, the enzyme responsible for processing APP to give the Nterminal portion of the Aβ peptide, is a membrane bound aspartyl protease consisting of an ectodomain catalytic unit, a Cterminal transmembrane segment and a cytoplasmic domain. Three BACE constructs, pET11a-BACE, pQE80L-BACE, and pQE70-BACE were designed to terminate at a position just before the transme Read More

With rapid increase in influenza A virus database, an important issue is whether the predictions are similar based on different datasets. Here we stratify 482 H3N2 hemagglutinins from influenza A virus in North America to different datasets. The predictions are made using logistic regression. The results show that the different datasets have significant impact on the predictions.

His-tagging is commonly used to aid and expedite the purification of recombinant proteins. It is commonly assumed, though less frequently tested, that the His-tag affects neither the structure nor the stability of the protein. Alanine:glyoxylate aminotransferase (AGT) is a peroxisomal pyridoxal 5'-phosphate (PLP) dependent enzyme which catalyzes the transamination of alanine and glyoxylate to pyruvate and glycine. AGT is a cli Read More

We have carried out a systematic analysis in order to evaluate whether Intra-Chain Disulfide Bridged Peptides (ICDBPs) observed in proteins of known three-dimensional structure adopt structurally similar conformations as they may correspond to structural/functional motifs. 406 representative ICDBPs comprising between 3 to 17 amino acid residues could be classified according to peptide sequence length and m Read More

P5 (KWKKLLKKPLLKKLLKKL-NH2) is an antibacterial 18-mer Leu-Lys rich peptide from CA (1-8)-MA (1-12) hybrid peptide (CA-MA). Here we show that decreasing the net hydrophobicity and charge of CA-MA by deleting Leu- or Lys- of the N- or C-terminal regions of P5 (P10 or P11). The antimicrobial activity of the peptides was measured by their growth inhibitory effect upon S. aureus, B. subtilis, P. aeruginosa, S. typhimu Read More

Utilizing different computational methods; phosphorylation, O-GlcNAc modification and Yin Yang sites are predicted in HMGN-1. Prediction results suggest that interplay of phosphorylation and O-GlcNAc modification regulates binding and removal of HMGN-1 with the nucleosome and its translocation from nucleus to cytoplasm and back to nucleus, consequently modulating gene expression.

In a permeablized cell system, oxidized cyt c is able to induce caspase cascade whereas reduced cyt c cannot. In in vitro experiments, oxidized cyt c can promote H2O2 generation. It is suggested that the redox state of cyt c might regulate the initiation of apoptosis via regulation of cellular ROS level.

We have observed that hamster prion protein (PrPC) undergoes conformational changes on exposure to heat or sonication. If a sonication induced new conformer is seeded with a small amount of its abnormal pathogenic isoform (PrPSc) it undergoes a significant conversion to a proteinase-resistant isoform. This suggests the presence of a third stable PrP conformer, which may be intermediate in the conversion of PrPC to PrPSc.

Bacillus licheniformis ??-amylase (BLA) is routinely used as a model thermostable amylase in biochemical studies. Its starch hydrolysis activity has recently been studied in Tris buffer. Here, we address the question that whether the application of Tris buffer may influence the results of BLA activity analyses. Based on the inhibition studies and docking simulations, we suggest that Tris molecule is a competitive inhibitor of star Read More

The current article describes the biophysical characterization and folding studies of fibroblast growth factor homologous factor-1b (FHF-1b) in comparison with acidic fibroblast growth factor (FGF-1). Our data indicates that FHF- 1 is significantly more stable than FGF-1. The folding mechanism of these two proteins seems to be different although they share high degree of sequence and structural similarity. FHF-1 unf Read More

We synthesized a Tat-related peptide acetyl-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Pro-Pro-Gln-Gly- Cys amide, Ac-Tat48-60-Gly-Cys-NH2, having high intracellular permeability, and conjugated this peptide to adenovirus vector to enhance gene transfer efficiency of adenovirus vector into cells. The peptide was prepared by the solid-phase peptide synthesis method and a bifunctional crosslinker 6-maleimidohexanoic acid N-hydro Read More

The number of atom-atom contacts in long distance can fit to the experimental binding energies in a dataset containing 151 experimental data with the correlation coefficient about 0.68. Based on this factor, a set of distancedependent empirical potentials for various types of short-distance (2.4 Å-5 Å) contacts was obtained by guided fitting, i.e. a set of two parameters fitting. Incorporation of these short-distance potentials impro Read More

Oxyntomodulin is a proglucagon-derived gut hormone that reduces food intake and body weight, thus represents a potential therapy for obesity. We synthesized and crystallized oxyntomodulin. The crystal diffracts x-ray to 2.4 Å resolution and belongs to space group P213 with unit-cell parameters a=b=c= 48.44 Å, α=β=γ=90°. Preliminary analysis indicates a trimer packing in one asymmetric unit.

To elucidate the molecular basis underlying their broad substrate specificity and reaction mechanism of the enzymes belonging to the haloacid dehalogenase (HAD) superfamily, TON_0559, a putative HAD subfamily protein from a hyperthermophilic archaeon Thermococcus onnurineus NA1, was expressed, purified and crystallized. X-ray diffraction data were collected to 2.0 Å resolution. The space group is C2, with unit cell pa Read More