Search results for "Protein Structure"

Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein

2019

JBC papers in press xx, 16604-16619 (2019). doi:10.1074/jbc.RA119.009845

Recombinant mussel protein Pvfp-5β: A potential tissue bioadhesive

2019

During their lifecycle, many marine organisms rely on natural adhesives to attach to wet surfaces for movement and self-defence in aqueous tidal environments. Adhesive proteins from mussels are biocompatible and elicit only minimal immune responses in humans. Therefore these proteins have received increased attention for their potential applications in medicine, biomaterials and biotechnology. The Asian green mussel Perna viridis secretes several byssal plaque proteins, molecules that help anchor the mussel to surfaces. Among these proteins, protein-5β (Pvfp-5β) initiates interactions with the substrate, displacing interfacial water molecules before binding to the surface. Here, we establis…

Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2

2016

We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …

Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates

2018

A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and ev…

2019

Mammalian fetuin-A and fetuin-B are abundant serum proteins with pleiotropic functions. Fetuin-B is a highly selective and potent inhibitor of metallopeptidases (MPs) of the astacin family, which includes ovastacin in mammals. By inhibiting ovastacin, fetuin-B is essential for female fertility. The crystal structure of fetuin-B was determined unbound and in complex with archetypal astacin, and it was found that the inhibitor has tandem cystatin-type modules (CY1 and CY2). They are connected by an exposed linker with a rigid, disulfide-linked `CPDCP-trunk', and are followed by a C-terminal region (CTR) with little regular secondary structure. The CPDCP-trunk and a hairpin of CY2 form a bipar…

Detecting Protein Aggregation on Cells Surface: Concanavalin A Oligomers Formation

2009

A number of neurodegenerative diseases involve protein aggregation and amyloid formation. Recently evidence has emerged indicating small-transient prefibrillar oligomers as the primary pathogenic agents. Noteworthy, strict analogies exist between the behaviour of cells in culture treated with misfolded non-pathogenic proteins and in pathologic conditions, this instance together with the observation that the oligomers and fibrils are characterised by common structural features suggest that common mechanisms for cytotoxicity could exists and have to be perused in common interactions involved in aggregation.We here report an experimental study on ConcanavalinA (ConA) aggregation and its effect…

FTIR spectroscopy studies of high pressure-induced changes in pork macromolecular structure

2019

Abstract High pressure processing (HPP) allows to extend the shelf life of meat and meat products by pressurization of microorganisms. At the same time, HPP can induce changes of the protein structure. Vacuum-packed pork chops were HPP-treated at 300, 600 MPa for 1 or 15 min. Samples of raw, cooked and HPP-treated meat muscles and juice were analysed to evaluate the structure of macromolecules. HPP caused visible discolouration of pork chops; hence, the colour of pork meat surface was tested. The lightness (colour component L*) was directly proportional to the applied pressure, probably due to the increased protein denaturation by high pressure. Pork meat muscle and juice samples were analy…

Regulation of ISWI chromatin remodelling activity.

2013

The packaging of the eukaryotic genome into chromatin facilitates the storage of the genetic information within the nucleus, but prevents the access to the underlying DNA sequences. Structural changes in chromatin are mediated by several mechanisms. Among them, ATP-dependent remodelling complexes belonging to ISWI family provides one of the best examples that eukaryotic cells evolved to finely regulate these changes. ISWI-containing complexes use the energy derived from ATP hydrolysis to rearrange nucleosomes on chromatin in order to favour specific nuclear reactions. The combination of regulatory nuclear factors associated with the ATPase subunit as well as its modulation by specific histo…

Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?

2002

p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein over-expression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 prote…

Aging, longevity, inflammation, and cancer.

2005

Cancer rates increase sharply with age in both sexes, and the majority of cases of cancer occur in patients over the age of 65 years. However, the incidence and mortality for cancer level off around 85-90 years of age, followed by a plateau, or even a decline in the last decades of life. Therefore, it seems reasonable to conclude that centenarians are endowed with a peculiar resistance to cancer. Tumor progression is a complex process that depends on interactions between tumor and host cells. One aspect of the host response, the inflammatory response, is of particular interest because it includes the release of proinflammatory cytokines, some of which may promote tumor growth and hence infl…