A5066210282- Antibiotic Resistance in Bacteria
- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Antibiotics Pharmacokinetics and Efficacy
- Microbial Natural Products and Biosynthesis
- Glycosylation and Glycoproteins Research
- Mycobacterium research and diagnosis
- Protein Structure and Dynamics
- Enzyme Production and Characterization
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Antimicrobial Resistance in Staphylococcus
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fungal and yeast genetics research
- Photosynthetic Processes and Mechanisms
- Synthesis of β-Lactam Compounds
- Immune Response and Inflammation
- Cancer therapeutics and mechanisms
- Immune Cell Function and Interaction
- Fungal Biology and Applications
- Biofuel production and bioconversion
- Enzyme-mediated dye degradation
- Bacteriophages and microbial interactions
Institut de Pharmacologie et de Biologie Structurale
2015-2025
Centre National de la Recherche Scientifique
2006-2023
Université Toulouse III - Paul Sabatier
2012-2023
Université de Toulouse
2011-2023
Wayne State University
1996-2002
University of Notre Dame
1999
École Polytechnique
1999
Wesleyan University
1998
University of Freiburg
1998
Laboratoire de Cristallographie et RMN Biologiques
1993-1996
β-Lactamases are the resistance enzymes for β-lactam antibiotics, of which four classes known. β-lactamases hydrolyze moieties these rendering them inactive. It is shown herein that class D OXA-10 β-lactamase depends critically on an unusual carbamylated lysine as basic residue both enzyme acylation and deacylation steps catalysis. The formation reversible. Evidence presented this dimeric in living bacteria. High-resolution x-ray structures native were determined at pH values 6.0, 6.5, 7.5,...
Bacteria resistant to antibiotics are being selected in a relatively short time, and cases of infections treatment by all known identified at alarming rates. The primary mechanism for resistance β-lactam is the catalytic function β-lactamases. However, imipenem (a β-lactam) resists action most β-lactamases virtually last effective agent against vancomycin-resistant Gram-positive bacteria, as well multiple antibiotic-resistant Gram-negative organisms. Here, we report crystal structure, 1.8 Å...
The crystal structure of the complex TEM-1 β-lactamase from Escherichia coli inhibited by 6α-(hydroxymethyl)penicillanic acid (1) is reported herein. This first for an acyl-enzyme intermediate with a substrate native class A β-lactamase. compound was designed and synthesized as molecule that would acylate active site enzyme, but resist deacylation virtue fact its C6α hydroxymethyl moiety expected to occupy space near hydrolytic water (J. Am. Chem. Soc. 1995, 117, 11055). species closely...
The crystal structure of a phosphonate complex the class A TEM-1 β-lactamase has been determined to resolution 2.0 Å. appears stoichiometrically at active site, bound covalently Ser70Oγ, with one phosphonyl oxygen in oxyanion hole. Although overall is very similar that native enzyme (rms difference 0.37 Å for all heavy atoms), changes have occurred position site functional groups. also not conformation observed another β-lactamase, Staphylococcus aureus PC1, same [Chen, C. H., et al. (1993)...
The treatment of infectious diseases by penicillin and cephalosporin antibiotics is continuously challenged the emergence dissemination numerous TEM SHV mutant β-lactamases with extended substrate profiles. These class A nevertheless remain inefficient against carbapenems, most effective clinically relevant pathogens. new member this enzyme class, NMC-A, was recently reported to hydrolyze at high rates, hence destroy, all known β-lactam antibiotics, including carbapenems cephamycins. crystal...
The mechanisms permitting nonpolymorphic CD1 molecules to present lipid antigens that differ considerably in polar head and aliphatic tails remain elusive. It is also unclear why hydrophobic motifs the of some antigens, which presumably embed inside pockets, contribute determinants for T-cell recognition. 1.9-Å crystal structure an active complex CD1b a mycobacterial diacylsulfoglycolipid presented here provides clues. Upon antigen binding, endogenous spacers CD1b, consist mixture...
InhA, an NAD‐dependent enoyl‐acyl carrier protein reductase, is involved in the biosynthesis of mycolic acids, specific lipids to mycobacteria. InhA target isoniazid, a first‐line anti‐tuberculosis drug used since 1950s. Isoniazid prodrug that needs be activated by catalase‐peroxidase KatG. Due resistance problems, substantial amount work has been carried out identify or design direct inhibitors demonstrating this enzyme still considered relevant for discovery new drugs. Much included...
β-Lactamases are resistance enzymes for β-lactam antibiotics. These hydrolyze the moieties of these antibiotics, rendering them inactive. Of four classes known β-lactamases, class D least understood. We report herein high-resolution (1.9 Å) crystal structure OXA-10 β-lactamase inhibited by a penicillanate derivative. The provides evidence that carboxylated Lys-70 (a carbamate) is intimately involved in mechanism enzyme.
CD1e is the only human CD1 protein existing in soluble form late endosomes of dendritic cells, where it facilitates processing glycolipid antigens that are ultimately recognized by CD1b-restricted T cells. The precise function remains undefined, thus impeding efforts to predict participation this presentation other antigens. To gain insight into its function, we determined crystal structure recombinant expressed cells at 2.90-Å resolution. revealed a groove less intricate than proteins, with...
The carboxysome is a bacterial micro-compartment (BMC) subtype that encapsulates enzymatic activities necessary for carbon fixation. Carboxysome shells are composed of relatively complex cocktail proteins, their precise number and identity being species dependent. Shell components can be classified in two structural families, the most abundant class associating as hexamers (BMC-H) supposed to major players regulating shell permeability. Up recently, these proteins were proposed associate...
Residue 104 is frequently mutated from a glutamic acid to lysine in the extended-spectrum TEM beta-lactamases responsible for resistance third-generation cephalosporins clinical Gram negative strains. Among class A beta-lactamases, it most variable residue within highly conserved loop which delineates one side of active site enzymes. To investigate role this phenotype, has been replaced by serine, threonine, lysine, arginine, tyrosine and proline. All these substitutions yield enzymes, with...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMass Spectral Kinetic Study of Acylation and Deacylation During the Hydrolysis Penicillins Cefotaxime by .beta.-Lactamase TEM-1 G238S MutantIsabelle Saves, Odile Burlet-Schiltz, Laurent Maveyraud, Jean-Pierre Samama, Jean-Claude Prome, Jean-Michel MassonCite this: Biochemistry 1995, 34, 37, 11660–11667Publication Date (Print):September 19, 1995Publication History Published online1 May 2002Published inissue 19 September...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThe First Structural and Mechanistic Insights for Class D β-Lactamases: Evidence a Novel Catalytic Process Turnover of β-Lactam AntibioticsDasantila Golemi, Laurent Maveyraud, Sergei Vakulenko, Samuel Tranier, Akihiro Ishiwata, Lakshmi P. Kotra, Jean-Pierre Samama, Shahriar MobasheryView Author Information Groupe de Cristallographie Biologique Institut Pharmacologie et Biologie Structurale du CNRS 205 route Narbonne, 31077-Toulouse Cedex,...
Clavulanate, an inhibitor for β-lactamases, was the very first antibiotic resistance enzyme that found clinical utility in 1985. The use of clavulanate and sulbactam tazobactam, which were introduced to clinic subsequently, has facilitated evolution a set β-lactamases not only retain their original function as enzymes but also are refractory inhibition by inhibitors. This article characterizes properties clinically identified M69L mutant variant TEM-1 β-lactamase from Escherichia coli,...