Gwen André

Gwen André
French National Institute for Agriculture, Food, and Environment (INRAE) | INRAE · Mathématique et Informatique Appliqués du Génome à l'Environnement

PhD HDR

About

68
Publications
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Introduction
I work as a structural computational biologist at Inra, on the Campus of Jouy-en-Josas, in MaIAGE: Applied Mathematics and Computer Science, from Genome to Environment headed by S. Schbath. My interests deal with computational screening of whole genomes and metagenomes to infer proteins structures and functional annotations. I have special focus on proteins of the gut microbiome which are involved in biomedical properties such as host-pathogen or anti-inflammatory signaling. It is mainly prokaryotic signaling through phosphorylation and dephosphorylation events, mediated by protein Ser/Thr kinases and protein Tyr phosphatases, respectively.

Publications

Publications (68)
Article
Full-text available
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), one of the deadliest infectious diseases. The alarming health context coupled with the emergence of resistant M. tuberculosis strains highlights the urgent need to expand the range of anti-TB antibiotics. A subset of anti-TB drugs in use are prodrugs that require bioactivatio...
Article
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Four serine/threonine kinases are present in all mycobacteria: PknA, PknB, PknG and PknL. PknA and PknB are essential for growth and replication, PknG regulates metabolism, but little is known about PknL. Inactivation of pknL and adjacent regulator MSMEG_4242 in rough colony M. smegmatis mc²155 produced both smooth and rough colonies. Upon restreak...
Article
Full-text available
The emergence of B. cereus as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with B. cereus infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, the molecular basis of these differences remain...
Article
Lactobacillus sakei is a nonpathogenic bacterial species exhibiting high fitness in heme-rich environments such as meat products, although it does not need iron or heme for growth. Heme capture and utilization capacities are often associated with pathogenic species and are considered virulence-associated factors in the infected hosts. For these rea...
Article
Objective The innate immune system plays a central role in osteoarthritis (OA). We identified 14-3-3ε as a novel mediator that guides chondrocytes toward an inflammatory phenotype. 14-3-3ε shares common characteristics with alarmins. These endogenous molecules, released into extracellular media, are increasingly incriminated in sustaining OA inflam...
Article
Full-text available
The transcriptional regulator PlcR, its cognate cell-cell signaling heptapeptide PapR7, and the oligopeptide permease OppABCDF, required for PapR7 import, form a quorum-sensing system that controls the expression of virulence factors in Bacillus cereus and Bacillus thuringiensis species. In B. cereus strain ATCC 14579, the transcriptional regulator...
Preprint
Full-text available
Lactobacillus sakei is a non-pathogenic lactic acid bacterium and a natural inhabitant of meat ecosystems. Although red meat is a heme-rich environment, L. sakei does not need iron or heme for growth, while possessing a heme-dependent catalase. Iron incorporation into L. sakei from myoglobin and hemoglobin was formerly shown by microscopy and the L...
Article
Full-text available
Protein phosphorylation especially on serine/threonine/tyrosine residues are frequent in many bacteria. This post-translational modification has been associated with pathogenicity and virulence in various species. However, only few data have been produced so far on generally recognized as safe bacteria used in food fermentations. A family of kinase...
Article
Forkhead-associated (FHA) domains are modules that bind to phosphothreonine (pThr) residues in signaling cascades. The FHA-containing mycobacterial protein GarA is a central element of a phosphorylation-dependent signaling pathway that redirects metabolic flux in response to amino acid starvation or cell growth requirements. GarA acts as a phosphor...
Article
Full-text available
Upon triggering by their inducer, signal transduction ATPases with numerous domains (STANDs), initially in monomeric resting forms, multimerize into large hubs that activate target macromolecules. This process requires conversion of the STAND conserved core (the NOD) from a closed form encasing an ADP molecule to an ATP-bound open form prone to mul...
Article
Full-text available
The synaptic protein SHANK3 encodes a multidomain scaffold protein expressed at the postsynaptic density of neuronal excitatory synapses. We previously identified de novo SHANK3 mutations in patients with autism spectrum disorders (ASD) and showed that SHANK3 represents one of the major genes for ASD. Here, we analyzed the pyramidal cortical neuron...
Article
Full-text available
Mycolic acids are essential components of the mycobacterial cell envelope and their biosynthetic pathway is a well-known source of antituberculous drug targets. Among the promising new targets in the pathway, FadD32 is an essential enzyme required for the activation of the long meromycolic chain of mycolic acids and essential for mycobacterial grow...
Article
Full-text available
Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified C...
Article
Full-text available
Galectins (Gals) constitute a family of mammalian lectins with affinity for beta-galactosides, characterized by the presence of conserved carbohydrate-recognition domains (CRDs). We have previously found that Gal-8, from tandem-repeat group with two linked CRDs, exerts two separate actions on CD4+ T cells: antigen-independent proliferation and, at...
Article
Full-text available
Osteoarthritis (OA) is a whole-joint disease characterized by progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the involvement of C...
Article
Iron is an essential element for bacterial growth and virulence. Because of its limited bioavailability in the host, bacteria have adapted several strategies to acquire iron during infection. In the human opportunistic bacteria Bacillus cereus, a surface protein IlsA is shown to be involved in iron acquisition from both ferritin and hemoproteins. I...
Article
Among hormone-inducible transcription factors, estrogen receptors (ERs) play important roles on tissue growth and differentiation, either by direct or indirect binding, in the nucleus, to specific DNA targets called estrogen responsive elements (EREs), or through non-genomic pathways. In human, two estrogen receptor isoforms (hERs), designated as h...
Article
Full-text available
Tuberculosis remains one of the world's deadliest human diseases, with a high prevalence of antibiotic-resistant Mycobacterium tuberculosis (Mtb) strains. A molecular understanding of processes underlying regulation and adaptation of bacterial physiology may provide novel avenues for the development of antibiotics with unconventional modes of actio...
Article
Osteoarthritis is a whole-joint disease characterized by the progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team previously identified 14-3-3 epsilon protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the...
Article
Among the few proteins shown to be secreted by the Tat system in Mycobacterium tuberculosis, Rv2525c is of particular interest, since its gene is conserved in the minimal genome of Mycobacterium leprae. Previous evidence linked this protein to cell wall metabolism and sensitivity to β-lactams. We describe here the crystal structure of Rv2525c that...
Article
Full-text available
Author Summary Our therapeutic arsenal to treat viral diseases is extremely limited, and there is a critical need for molecules that could be used against multiple viruses. Among possible strategies, there is a growing interest for molecules stimulating cellular defense mechanisms. We recently developed a functional assay to identify stimulators of...
Article
Full-text available
The neural cell-adhesion molecules contactin 4, contactin 5 and contactin 6 are involved in brain development, and disruptions in contactin genes may confer increased risk for autism spectrum disorders (ASD). We describe a co-culture of rat cortical neurons and HEK293 cells overexpressing and delivering the secreted forms of rat contactin 4-6. We q...
Article
Full-text available
We characterized a new quorum-sensing regulator, PlcRa, which is present in various members of the B. cereus group and identified a signaling heptapeptide for PlcRa activity: PapRa(7). We demonstrated that PlcRa is a 3D structural paralog of PlcR using sequence analysis and homology modeling. A comparison of the transcriptomes at the onset of stati...
Data
Identification of a motif common to the promoter regions of putative CymR targets in the B. cereus ATCC 14579 strain. An alignment of the promoter regions of the ssuB, yrrT, tcyP, luxS, cysK, cysH and BC1090 genes is presented. The consensus sequence for the CymR-binding site was determined with the WebLogo tool. (PPTX)
Data
Kinetics of cymR gene expression. β-galactosidase specific activity (U/mg protein) of the wild-type (black circles), ΔplcRa (white triangles) strains harboring the transcriptional PcymR’-lacZ fusion, in LB. Errors bars are shown. Time zero corresponds to the onset of the stationary growth phase, and tn is the number of hours before (–) or after tim...
Data
Reconstruction of the sulfur metabolism pathway in B. cereus: transport and biosynthesis of sulfur-containing amino acids. The putative proteins involved in the uptake and assimilation of inorganic (sulfate) and organic sulfur sources (sulfonates, cystine, methionine) are indicated by the corresponding genes. The BC numbers (ATCC 14579 strain) for...
Data
Kinetics of plcRa gene expression. β-galactosidase specific activity (U/mg protein) of the wild-type strain harboring the transcriptional PplcRa’-lacZ fusion, in LB medium without or with hydrogen peroxide (0.4 mM) or diamide (10 mM). Hydrogen peroxide or diamide was added at an OD of 2 (∼t−0.3). Errors bars are shown. (PPTX)
Data
a. Genes with differences of 0.33 fold of less are presented. b. Locus tag in type strain ATCC 14579. c. The gene names indicated correspond to B. subtilis homologs, with the exception of hblB, hblL1, hblL2 which correspond to gene names in B. cereus. *These genes were also analysed with qRT-PCR at t1 and the expression ratio was 0.1. (DOC)
Conference Paper
Background / Purpose: Ruminococcus gnavus is a Firmicutes gut symbiont present in healthy humans, as an integral part of the mucosa-associated bacterial consortium. Previous work has shown that R. gnavus E1 expresses a putative GH36 alpha -galactosidase (AgaE1) when in a symbiotic relationship with a rodent host.Here we show that recombinant AgaE...
Data
Superimposition of the different monomer structures of the breakage-reunion domain. M. tuberculosis DNA gyrase GA57BK (3IFZ) (this work) in light green, M. tuberculosis DNA gyrase MtGyrA59 (3ILW, 25) in pale green, E. coli DNA gyrase (1AB4) (36) in dark green, S. pneumoniae topoisomerase IV (2NOV) (33) in red, S. aureus topoisomerase IV (2INR) (34)...
Data
Structure-based sequence alignment of the Toprim domain from type II topoisomerases. The sequence names are as follows: MtGyr (PDB code 3IFZ) (this work), M. tuberculosis DNA gyrase; SpTopIV (PDB code 3FOF) (26), S. pneumoniae topoisomerase IV and ScTopII (PDB code 2RGR) (29), S. cerevisiae topoisomerase II. alpha-helices (cylinders) and beta-stran...
Data
The three different conformations of the breakage-reunion domain. A. The breakage-reunion domain of M. tuberculosis (PDB id 3IFZ) (this work), representing the closed conformation with the DNA-gate and the C-gate closed. This closed conformation is also observed in the E. coli DNA gyrase (36), S. pneumoniae and S. aureus topoisomerase IV breakage-r...
Data
Structure-based sequence alignment of the breakage-reunion domain from type II topoisomerases. The sequence names are as follows: MtGyr (PDB code 3IFZ) (this work), M. tuberculosis DNA gyrase; EcGyr (PDB code 1AB4) (36), E. coli DNA gyrase; SaTopIV (PDB code 2INR) (34), S. aureus topoisomerase IV; SpTopIV (PDB code 2NOV) (33), S. pneumoniae topoiso...
Data
Values of the interfaces calculated by PISA for the five structures of the breakage-reunion domain dimer in closed conformation. The PDB codes for the five structures are given: 3IFZ (this work) and 3ILW (25) correspond to M. tuberculosis DNA gyrase, 1AB4 (36) to E. coli DNA gyrase, 2INR (34) to S. aureus topoisomerase IV, 2NOV (33) to S. pneumonia...
Article
Full-text available
Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechan...
Article
Penicillium griseofulvum possesses two endo-(1,4)-beta-xylanase genes, PgXynA and PgXynB, belonging to family 11 glycoside hydrolases. The enzymes share 69% identity, a similar hydrolysis profile i.e. the predominant production of xylobiose and xylotriose as end products from wheat arabinoxylan and a specificity region of six potential xylose subsi...
Article
Fork-head associated (FHA) domains are widely found in bacteria, but their cellular functions remain unclear. Here, we focus on Mycobacterium tuberculosis GarA, an FHA-containing protein conserved in actinomycetes that is phosphorylated by different Ser/Thr protein kinases. Using various physicochemical approaches, we show that phosphorylation sign...
Article
Endopolygalacturonases (EndoPGs) hydrolyse the 1-4 linkages between two alpha-d-galacturonic acids (GalA) of the smooth homogalacturonan regions of pectin. GalA may be methyl-esterified on the carboxylic group and acetyl-esterified on the hydroxylic groups. EndoPG activity most often decreases with such increasing degree of substitution. In this pa...
Article
Penicillium griseofulvum xylanase (PgXynA) belongs to family 11 glycoside hydrolase. It exhibits unique amino acid features but its three-dimensional structure is not known. Based upon the X-ray structure of Penicillium funiculosum xylanase (PfXynC), we generated a three-dimensional model of PgXynA by homology modeling. The native structure of PgXy...
Article
Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and virulence of Mycobacterium tuberculosis, the etiological agent of tuberculosis. This pathogen...
Article
Amylosucrase from Neisseria polysaccharea (AS) is a transglucosidase from the glycoside-hydrolase family 13 that catalyzes the synthesis of an amylose-like polymer from sucrose, without any primer. Its affinity towards glycogen is particularly noteworthy since glycogen is the best D-glucosyl unit acceptor and the most efficient activator (98-fold k...
Chapter
Despite the fact that the a-amylase family (GH 13) displays a similar (α/β)8 architecture and a consensus α-retaining mechanism on the a-D-glucose polymer, the whole family of a-amylase enzymes displays a wide range of reactions. Our hypothesis is that hydrolysis vs transglycosylation could be governed by specific amino-acid residues located at sub...
Article
Full-text available
Arabinan and galactan side chains of sugar beet pectins are esterified by ferulic acid residues that can undergo in vivo oxidative reactions to form dehydrodiferulates. After acid and enzymatic degradation of sugar beet cell walls and fractionation of the solubilized products by hydrophobic interaction chromatography, three dehydrodiferulate-rich f...
Article
Full-text available
The structures of complexes of Fusarium moniliforme endopolygalacturonase (endoPG) with non-methylated or partly methylated homogalacturonan fragments were modeled to identify the residues involved in substrate binding and to correlate the cleavage pattern with the experimental productive modes. The conformational space of the complex was extensive...
Article
Alpha-amylases are widespread endo-enzymes involved in the hydrolysis of internal alpha-(1,4) glycosidic linkages of starch polymers. Molecular modeling of amylose-amylase interactions is a step toward enzymatic mechanism understanding and rational design of new enzymes. From the crystallographic complex of barley alpha-amylase AMY2-acarbose, the s...
Article
Full-text available
The role in activity of outer regions in the substrate binding cleft in-amylases is illustrated by mutational analysis of Tyr 105 and Thr 212 localized at subsites 6 and 4 (substrate cleavage occurs between subsites 1 and 1) in barley-amylase 1 (AMY1). Tyr 105 is conserved in plant-amylases whereas Thr 212 varies in these and related enzymes. Compa...
Article
In the first two papers of this series, the tools necessary to evaluate substrate ring deformations were developed, and then the modeling of short amylose fragments (maltotriose and maltopentaose) inside the catalytic site of barley alpha-amylase was performed. In this third paper, this docking has been extended to the whole catalytic cleft. A syst...
Article
In the first paper of this series, the tools necessary to evaluate the consequences of glucopyranose ring deformations in terms of glycosidic torsion angle shifts, and amylose chain propagation have been created. In this second paper, the modeling of amylose fragments into the catalytic region of barley-amylase has been performed by a systematic ap...
Article
In the first paper of this series, the tools necessary to evaluate the consequences of glucopyranose ring deformations in terms of glycosidic torsion angle shifts, and amylose chain propagation have been created. In this second paper the modeling of amylose fragments into the catalytic region of barley barley alpha-amylase has been performed by a s...
Article
In the presence of steric constraints, flexible forms, i.e., skew (S), boat (B) or half-boat (H), were evoked from experimental data and conformational analyses by molecular mechanics calculations for glucopyranose rings of amylose fragments. This important case, occurring, for example, in amylose-amylase complexes, requires careful analysis of the...

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