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Florence Pojer

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Publications associées (48)

Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein

Henning Paul-Julius Stahlberg, David Hacker, Florence Pojer, Kelvin Ka Ching Lau, Dongchun Ni

The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, ...

2020

Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1)

Pierre Vogel, Florence Pojer, Somi Reddy Majjigapu

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative disea ...

AMER CHEMICAL SOC2019

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

Florence Pojer, Oliver Hantschel, Tim Kükenshöner, Nadine Eliane Schmit

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant c ...

Elsevier2017

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Florence Pojer, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Delphine Maude Tardivon, Sina Maren Reckel, Barbara Gerig, Tim Kükenshöner, Sara Raquel Pereira Pinho, Charlotte Julie Caroline Gehin

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017

A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria

John McKinney, Florence Pojer, Matteo Dal Peraro, Tarun Chopra, Paul Murima, Giulia Fonti

Fatty acid metabolism is an important feature of the pathogenicity of Mycobacterium tuberculosis during infection. Consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative TCA cycle and the glyoxylate shunt. In Escher ...

Nature Publishing Group2016

Internalization and vacuolar targeting of the brassinosteroid hormone receptor BRI1 are regulated by ubiquitination

Florence Pojer

Brassinosteroids are plant steroid hormones that control many aspects of plant growth and development, and are perceived at the cell surface by the plasma membrane-localized receptor kinase BRI1. Here we show that BRI1 is post-translationally modified by K ...

Nature Publishing Group2015

2-Carboxyquinoxalines Kill Mycobacterium tuberculosis through Noncovalent Inhibition of DprE1

Gaëlle Séraphine Kolly, Stewart Cole, Neeraj Dhar, Florence Pojer, Ruben Hartkoorn, Joao Pedro De Almeida Neres

Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 mu M, ...

American Chemical Society2015

Lansoprazole is an antituberculous prodrug targeting cytochrome bc1

Stewart Cole, Claudia Sala, Florence Pojer, Philippe Busso, Jan Lars Rybniker, Anthony Vocat, Andrej Benjak

Better antibiotics capable of killing multi-drug-resistant Mycobacterium tuberculosis are urgently needed. Despite extensive drug discovery efforts, only a few promising candidates are on the horizon and alternative screening protocols are required. Here, ...

Nature Publishing Group2015

Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure-activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose 2 '-oxidase

Stewart Cole, Florence Pojer, Anirban Ghosh, Joao Pedro De Almeida Neres

We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of deca ...

Elsevier2015

Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis

Stewart Cole, Florence Pojer, Aleksandre Japaridze, Jérémie Piton

Mycobacterium tuberculosis secretes multiple virulence factors during infection via the general Sec and Tat pathways, and via specialized ESX secretion systems, also referred to as type VII secretion systems. The ESX-1 secretion system is an important viru ...

Elsevier2015

Functional Dissection of Intersubunit Interactions in the EspR Virulence Regulator of Mycobacterium tuberculosis

Giovanni Dietler, Benjamin Blasco, Stewart Cole, Florence Pojer, Matteo Dal Peraro, Basile Isidore Martin Wicky, Aleksandre Japaridze, Marco Stenta

The nucleoid-associated protein EspR, a chromosome organizer, has pleiotropic effects on expression of genes associated with cell wall function and pathogenesis in Mycobacterium tuberculosis. In particular, EspR binds to several sites upstream of the espAC ...

American Society for Microbiology2014

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

Rudolf Hovius, Christian Heinis, Florence Pojer, Shiyu Chen, Ranganath Gopalakrishnan

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with ...

Nature Publishing Group2014

The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron sulfur cluster biogenesis and oxidative stress defence

Gaëlle Séraphine Kolly, Stewart Cole, Florence Pojer, Jeffrey Chen, Jan Lars Rybniker

The complex multiprotein systems for the assembly of protein-bound iron sulfur (Fe S) clusters are well defined in Gram-negative model organisms. However, little is known about Fe S cluster biogenesis in other bacterial species. The ISC (iron sulfur cluste ...

Portland Press2014

Pyridomycin bridges the NADH- and substratebinding pockets of the enoyl reductase InhA

Stewart Cole, Florence Pojer, Ruben Hartkoorn, Joao Pedro De Almeida Neres

Pyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-bi ...

Nature Publishing Group2014

Towards a new combination therapy for tuberculosis with next generation benzothiazinones

Paul Joseph Dyson, Thierry Buclin, Stewart Cole, Florence Pojer, Ruben Hartkoorn, Ming Zhang, Benoit Lechartier, Joao Pedro De Almeida Neres, Anthony Vocat

The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) a ...

2014

The Crystal Structures of Apo and cAMP-Bound GlxR from Corynebacterium glutamicum Reveal Structural and Dynamic Changes upon cAMP Binding in CRP/FNR Family Transcription Factors

Stewart Cole, Florence Pojer

The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in ...

Public Library of Science2014

Phenotypic Profiling of Mycobacterium tuberculosis EspA Point Mutants Reveals that Blockage of ESAT-6 and CFP-10 Secretion In Vitro Does Not Always Correlate with Attenuation of Virulence

Stewart Cole, Anna De Graff Tischler, Neeraj Dhar, Florence Pojer, Jeffrey Chen, Ming Zhang, Jan Lars Rybniker

The EspA protein of Mycobacterium tuberculosis is essential for the type VII ESX-1 protein secretion apparatus, which delivers the principal virulence factors ESAT-6 and CFP-10. In this study, site-directed mutagenesis of EspA was performed to elucidate it ...

American Society for Microbiology2013

Tetrahydrobiopterin Biosynthesis as an Off-Target of Sulfa Drugs

Kai Johnsson, Florence Pojer, Miriam Grønlund Pedersen, Hirohito Haruki, Katarzyna Irena Gorska

The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamet ...

American Association for the Advancement of Science2013

Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence

Stewart Cole, Neeraj Dhar, Florence Pojer, Jeffrey Chen, Ming Zhang, Stefanie Boy-Röttger, Jan Lars Rybniker

The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal ...

Wiley-Blackwell2013

Structure and function of the transketolase from Mycobacterium tuberculosis and comparison with the human enzyme

Stewart Cole, Florence Pojer, Elizabeth Fullam

The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketola ...

Royal Soc2012

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