Search results for "binding site"
showing 10 items of 856 documents
Critical Structural Defects Explain Filamin A Mutations Causing Mitral Valve Dysplasia
2019
Mitral valve diseases affect approximately 3% of the population and are the most common reasons for valvular surgery because no drug-based treatments exist. Inheritable genetic mutations have now been established as the cause of mitral valve insufficiency, and four different missense mutations in the filamin A gene (FLNA) have been found in patients suffering from non-syndromic mitral valve dysplasia (MVD). The FLNA protein is expressed, in particular, in endocardial endothelia during fetal valve morphogenesis and is key in cardiac development. The FLNA-MVD causing mutations are clustered in the N-terminal region of FLNA. How the mutations in FLNA modify its structure and function, have mos…
Linked Analysis of Large Cooperative, Allosteric Systems: The Case of the Giant HBL Hemoglobins
2008
Homotropic and heterotropic allosteric interactions are important mechanisms that regulate protein function. These mechanisms depend on the ability of oligomeric protein complexes to adopt different conformations and to transmit conformation-linked signals from one subunit of the complex to the neighboring ones. An important step in understanding the regulation of protein function is to identify and characterize the conformations available to the protein complex. This task becomes increasingly challenging with increasing numbers of interacting binding sites. However, a large number of interacting binding sites allows for high homotropic interactions (cooperativity) and thus represents the m…
Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation
2021
Metal complexes can be considered a "paradigm of promiscuity" when it comes to their interactions with proteins. They often form adducts with a variety of donor atoms in an unselective manner. We have characterized the adducts formed between a series of isostructural N-heterocyclic carbene (NHC) complexes with Ru, Os, Rh, and Ir centers and the model protein hen egg white lysozyme by X-ray crystallography and mass spectrometry. Distinctive behavior for the metal compounds was observed with the more labile Ru and Rh complexes targeting mainly a surface l-histidine moiety through cleavage of p-cymene or NHC co-ligands, respectively. In contrast, the more inert Os and Ir derivatives were detec…
Global transcriptional profiling ofCandida albicans cwt1 null mutant
2007
CaCwt1p is a Candida albicans putative transcriptional factor homologue to Rds2p in Saccharomyces cerevisiae. The lack of this protein in S. cerevisiae leads to a pleiotropic resistance to drugs and defects in cell wall architecture that are also detectable in C. albicans. It is also known that CaCwt1p is mainly expressed in the stationary growth phase of this fungus. In order to elucidate the role of CWT1, transcriptome analysis of the mutant strain was performed in exponential and stationary growth phases. A total of 460 genes were found to be up- or downregulated in the mutant strain growing exponentially, and 666 genes presented a misregulation when cwt1 cells reached the stationary pha…
Identification of Rothia Bacteria as Gluten-Degrading Natural Colonizers of the Upper Gastro-Intestinal Tract
2011
Background Gluten proteins, prominent constituents of barley, wheat and rye, cause celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and the protease-resistant domains contain multiple immunogenic epitopes. The aim of this study was to identify novel sources of gluten-digesting microbial enzymes from the upper gastro-intestinal tract with the potential to neutralize gluten epitopes. Methodology/Principal Findings Oral microorganisms with gluten-degrading capacity were obtained by a selective plating strategy using gluten agar. Microbial speciations were carried out by 16S rDNA gene sequencing. Enzyme activities wer…
Antagonists and agonists at the glycine site of the NMDA receptor for therapeutic interventions.
2003
For decades neuroreceptor research has focused on the development of NMDA glycine-site antagonists, after Johnson and Ascher found out in 1987 about the co-agonistic character of this achiral amino acid at the NMDA receptor. Contrary to the inhibitory glycine receptor (glycine(A)) the glycine binding site on the NMDA receptor (glycine(B)) is strychnine-insensitive. A great diversity of diseases showing a disturbed glutamate neurotransmission have been linked to the NMDA receptor. Glycine site antagonists have been investigated for acute diseases like stroke and head trauma as well as chronic ones like dementia and chronic pain.
Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids.
2000
SUMMARY SP-A is found principally in the lung, and has been associated with lamellar bodies also found in the synovial joint. Both SP-A and C1q contain collagen-like regions, and SP-A and C1q have some structural similarities, both having a globular head region and a collagen-like tail. Here we are able to show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantibodies, is present in synovial fluid (SF) isolated from patients with rheumatoid arthritis (RA); (ii) in absorption experiments only a limited degree of cross-reactivity between autoantibodies reactive with C1q and SP-A is observed; (iii) there is no cross-reactivity between autoantibodies reactive with type II coll…
Local dynamics of DNA probed with optical absorption spectroscopy of bound ethidium bromide
1997
We have studied the local dynamics of calf thymus double-helical DNA by means of an "optical labeling" technique. The study has been performed by measuring the visible absorption band of the cationic dye ethidium bromide, both free in solution and bound to DNA, in the temperature interval 360-30 K and in two different solvent conditions. The temperature dependence of the absorption line shape has been analyzed within the framework of the vibronic coupling theory, to extract information on the dynamic properties of the system; comparison of the thermal behavior of the absorption band of free and DNA-bound ethidium bromide gave information on the local dynamics of the double helix in the prox…
Interaction between flavour compounds and beta-lactoglobulin: approach by NMR and 2D/3D-QSAR studies of ligands
2004
author cannot archive publisher's version/PDF; International audience; Interactions between flavour compounds and beta-lactoglobulin (BLG) have been the subject of several studies, but there are no unanimous binding site explanations. In our laboratory, interactions between BLG, and two flavour compounds, beta-ionone and gamma-decalactone, were studied by 2D-NMR spectroscopy. It appears that several amino acids affected by binding of gamma-decalactone are buried in the central cavity, whereas binding of beta-ionone affects amino acids located in a groove near the outer surface of the protein. 2D/3D-QSAR studies were performed using QSAR+ module of Cerius2 and Catalyst. The QSAR equation pr…
Interactions entre la beta-lactoglobuline et les arômes : impact au niveau moléculaire
2008
Interactions between β-lactoglobulin (BLG) and aroma compounds were investigated by complementary techniques for a better knowledge of binding mechanisms between proteins and aroma compounds at a molecular scale. Two binding sites have been defined for the monomeric BLG, one internal site within the central calyx, and one external site between the calyx and the α helix. In a first step, a relation between the ligand structure and its binding behaviour was established from the study of impact of a wide range of aroma compounds on the structure of native BLG. We evidenced at least two binding behaviours as a function of the chemical class, the hydrophobicity, or the structure of the ligands. …