A5087308606- Enzyme Production and Characterization
- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Pancreatitis Pathology and Treatment
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Natural Antidiabetic Agents Studies
- Crystallization and Solubility Studies
- Steroid Chemistry and Biochemistry
- Microbial Natural Products and Biosynthesis
- Retinoids in leukemia and cellular processes
- Enzyme Structure and Function
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Biofuel production and bioconversion
- Polysaccharides and Plant Cell Walls
- Drug Transport and Resistance Mechanisms
- Chemical Synthesis and Analysis
- Hormonal and reproductive studies
- Lipid Membrane Structure and Behavior
- Phytase and its Applications
- Glycosylation and Glycoproteins Research
- Aldose Reductase and Taurine
- Bacterial Genetics and Biotechnology
Institut de Pharmacologie et de Biologie Structurale
2014-2022
Université de Toulouse
2014-2021
Centre National de la Recherche Scientifique
2000-2021
Université Toulouse III - Paul Sabatier
2014-2021
Centre National pour la Recherche Scientifique et Technique (CNRST)
2014
Centre National de la Recherche Scientifique et Technologique
2014
Drexel University
2009-2014
Université de Montpellier
2007-2008
Inserm
2007-2008
Centre de Biologie Structurale
2007-2008
Retinoid X receptors (RXRα, -β, and -γ) occupy a central position in the nuclear receptor superfamily, because they form heterodimers with many other family members hence are involved control of variety (patho)physiologic processes. Selective RXR ligands, referred to as rexinoids, already used or being developed for cancer therapy have promise treatment metabolic diseases. However, important side effects remain associated existing rexinoids. Here we describe rational design functional...
Crystal structures of human pancreatic α-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide the trestatin family produced identical continuous electron densities corresponding to pentasaccharide species, spanning -3 +2 subsites enzyme, presumably resulting from transglycosylation. Binding acarviosine core linked glucose residue at -1 appears be critical part interaction process between α-amylases...
Steroids are implicated in many physiological processes, such as reproduction, aging, metabolism, and cancer. To understand the molecular basis for steroid recognition discrimination, we studied human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) responsible last step bioactivation of all estrogens. Here report first observation conversion dihydrotestosterone (DHT) into 3beta,17beta-androstanediol (3beta-diol) by 17beta-HSD1, an enzyme more than half a century. Kinetic...
α-L-arabinofuranosidases are glycoside hydrolases that specifically hydrolyze non-reducing residues from arabinose-containing polysaccharides. In the case of arabinoxylans, which main components hemicellulose, they part microbial xylanolytic systems and necessary for complete breakdown arabinoxylans. Glycoside hydrolase family 62 (GH62) is currently a small contains only bacterial fungal members. Little known about GH62 mechanism action, because few members have been biochemically...
Mammalian α-amylases catalyze the hydrolysis of α-linked glucose polymers according to a complex processive mechanism. We have determined X-ray structures porcine pancreatic α-amylase complexes with smallest molecule trestatin family (acarviosine-glucose) which inhibits and yet is not hydrolyzed by enzyme. A structure analysis at 1.38 Å resolution this allowed for clear identification genuine single hexasaccharide species composed two α-1,4-linked original molecules bound active site The...
The human pregnane X receptor (hPXR) is a nuclear that regulates the expression of phase I and II drug-metabolizing enzymes as well drug transporters. In addition, this plays critical role in cholesterol homeostasis protecting tissues from potentially toxic endobiotics. hPXR activated by broad spectrum low-affinity compounds including xenobiotics endobiotics such bile acids their precursors. Crystallographic studies revealed ligand binding domain (LBD) with large conformable pocket likely to...
Many large natural product antibiotics act by specifically binding and sequestering target molecules found on bacterial cells. We have developed a new strategy to expedite the structural analysis of such antibiotic-target complexes, in which we covalently link carrier proteins, then crystallize entire carrier-target-antibiotic complex. Using native chemical ligation, linked Lys-D-Ala-D-Ala epitope for glycopeptide three different proteins. show that recognition this peptide multiple is not...
The first crystallographic structure of human type 3 3α-hydroxysteroid dehydrogenase (3α-HSD3, AKR1C2), an enzyme playing a critical role in steroid hormone metabolism, has been determined complex with testosterone and NADP at 1.25-Å resolution. enzyme's 17β-HSD activity was studied comparison its 3α-HSD activity. catalyzes the inactivation dihydrotestosterone into 5α-androstane-3α,17β-diol (3α-diol) as well transformation androstenedione testosterone. Using our homogeneous highly active...
A fluorescence-based technique for detecting protein-lipid interactions may aid development of drugs that disrupt these regulatory interactions.
Pig pancreatic α-amylase (PPA), an enzyme belonging to the family, is involved in degradation of starch. Like some other members this PPA requires chloride reach maximum activity levels. To further explain mechanism activation, a crystal wild-type soaked with maltopentaose using chloride-free buffer was analyzed by X-ray crystallography. A conspicuous reorientation acid/base catalyst Glu233 residue found occur. The structural results, along kinetic data, show that maintained active site,...
The alpha-amylase from Tenebrio molitor larvae (TMA) has been crystallized in complex with the inhibitor (alpha-AI) bean Phaseolus vulgaris. A molecular-replacement solution of structure was obtained using refined pig pancreatic (PPA) and alpha-AI atomic coordinates as starting models. structural analysis showed that although TMA typical common to alpha-amylases, large deviations mammalian models occur loops. Despite these differences interacting loops, is still able inhibit both insect...
Antimicrobial drug resistance is a serious public health problem and the development of new antibiotics has become an important priority. Ristocetin A class III glycopeptide antibiotic that used in diagnosis von Willebrand disease which served as lead compound for antimicrobial therapeutics. The 1.0 resolution crystal structure complex between ristocetin bacterial cell-wall peptide been determined. As observed most other antibiotics, it shown forms back-to-back dimer containing concave...
Oomycetes are microorganisms that distantly related to true fungi and many members of this phylum major plant pathogens. express proteins able interact with cell wall polysaccharides, such as cellulose. This interaction is thought be mediated by carbohydrate-binding modules classified into CBM family 1 in the CAZy database. In study, two CBMs (1-1 1-2) form part glycoprotein, CBEL, from Phytophthora parasitica have been submitted detailed characterization, first better quantify their...
Steroid hormones play an essential role in a wide range of physiological and pathological processes, such as growth, metabolism, aging, hormone-sensitive cancers. Estrogens are no exception influence differentiation, functioning many target tissues, the mammary gland, uterus, hypothalamus, pituitary, bone, liver. Although very similar structure, each steroid class (i.e., estrogens, androgens, progestins, mineral corticoids, or glucocorticoids) is responsible for distinct processes. To permit...
Crystal structures of human pancreatic α-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide the trestatin family produced identical continuous electron densities corresponding to pentasaccharide species, spanning -3 +2 subsites enzyme, presumably resulting from transglycosylation. Binding acarviosine core linked glucose residue at -1 appears be critical part interaction process between α-amylases...
Tuberculosis (TB) remains a global health crisis, further exacerbated by the slow pace of new treatment options, and emergence extreme total drug resistance to existing drugs. The challenge developing antibacterial compounds with activity against Mycobacterium tuberculosis (Mtb), causative agent TB, is in part due unique features this pathogen, especially composition structure its complex cell envelope. Therefore, targeting enzymes involved envelope synthesis has been major interest for...
Two errors in sugar stereochemistry the structure of ristocetin A have been corrected and has re-refined.
Mycobacterium tuberculosis is the causative agent of disease, which claims more human lives each year than any other bacterial pathogen. M. and mycobacterial pathogens have developed a range unique features that enhance their virulence promote survival in host. Among these lies particular cell envelope with high lipid content, plays substantial role pathogenicity. Several components mycobacteria, e.g., mycolic acids, phthiocerol dimycocerosates, phenolic glycolipids, belong to "family"...
In androgen-sensitive target tissues, 3 alpha-hydroxysteroid dehydrogenase regulates the androgen receptor (AR) activity by catalyzing inactivation of 5 alpha-dihydrotestosterone (the most natural potent androgen) to alpha-androstane-3 alpha,17 beta-diol. this report, crystallization a human prostatic type dehydrogenase, member aldo-keto reductase superfamily, is described. Two different crystal forms complex between alpha-HSD, NADP(+) and testosterone have been obtained using PEG as...