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Florence Pojer

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Publications associées (48)

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A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria

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

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

Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins

Bruno Emanuel Ferreira De Sousa Correia, Luc Reymond, Florence Pojer, Elisa Oricchio, Sandrine Madeleine Suzanne Georgeon, Kelvin Ka Ching Lau, Sarah Wehrle, Aaron Simone Petruzzella, Natalya Katanayeva, Albert Santamaria Martinez, Marine Jeanne Françoise Bruand

Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterio ...

Nature Portfolio2024

Directed evolution of the suicide protein O⁶-alkylguanine-DNA alkyltransferase for increased reactivity results in an alkylated protein with exceptional stability

Ursula Röthlisberger, Kai Johnsson, Florence Pojer, Elizabeth Claire Brunk, Birgit Mollwitz, Simone Schmitt

Here we present a biophysical, structural, and computational analysis of the directed evolution of the human DNA repair protein O-6-alkylguanine-DNA alkyltransferase (hAGT) into SNAP-tag, a self-labeling protein tag. Evolution of hAGT led not only to incre ...

2012

Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein

Stewart Cole, Jacques Rougemont, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Swapna Uplekar, Benjamin Blasco

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or neg ...

Public Library of Science2012

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

Stewart Cole, Florence Pojer

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

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

High-affinity peptides developed against calprotectin and their application as synthetic ligands in diagnostic assays

Christian Heinis, Florence Pojer, Kelvin Ka Ching Lau, Cristina Diaz Perlas, Lluc Farrera Soler

A peptide was developed that binds to calprotectin, a marker of major inflammatory disorders, and found to be suited for diagnostic tests. The use of synthetic peptides in assays is of great interest due to their high precision, robustness and low price. ...

Nature Portfolio2023

Sigma Factor F does not Prevent Rifampin Inhibition of RNA Polymerase or Cause Rifampin Tolerance in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Sophie Magnet

The tolerance of Mycobacterium tuberculosis to anti-tuberculosis drugs is a major reason for the lengthy therapy needed to treat a tuberculosis infection. Rifampin is a potent inhibitor of RNA polymerase (RNAP) in vivo, but has been shown to be less effect ...

American Society for Microbiology2010

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid

Stewart Cole, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Swapna Uplekar, Joao Pedro De Almeida Neres, Raju Mukherjee, Sophie Magnet

Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an importan ...

Wiley Open Access2012

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

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

Stewart Cole, Florence Pojer, Gaëlle Séraphine Kolly, 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

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

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

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

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Matteo Dal Peraro, Oliver Hantschel, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Allan Joaquim Lamontanara, Grégory La Sala, Tim Kükenshöner, Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys

Didier Trono, Henning Paul-Julius Stahlberg, Priscilla Turelli, Florence Pojer, Kelvin Ka Ching Lau, Charlène Mireille Raymonde Raclot, Myriam Isabelle Lamrayah, Yoan Désiré Duhoo, Jérémy Campos, Vanessa Genet

Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutrali ...

2023

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

Pierre Vogel, Florence Pojer, Somi Reddy Majjigapu, Aline Emma Christine Reynaud

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

Azole-Based Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors

Pierre Vogel, George Coukos, Florence Pojer, Somi Reddy Majjigapu, Aline Emma Christine Reynaud

The heme enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays an essential role in immunity, neuronal function, and aging through catalysis of the rate-limiting step in the kynurenine pathway of tryptophan metabolism. Many IDO1 inhibitors with different chemo ...

AMER CHEMICAL SOC2021

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, Neeraj Dhar, Florence Pojer, Ming Zhang, Jan Lars Rybniker, Anna De Graff Tischler

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

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

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

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

Towards anti-virulence drugs targeting ESX-1 mediated pathogenesis of Mycobacterium tuberculosis

Stewart Cole, Florence Pojer, Benjamin Blasco

Mycobacterium tuberculosis (M. tb) the causative agent of tuberculosis (TB) causes 1.7 million deaths annually. According to the World Health Organization, in some areas of the world, 25% of TB cases are due to multi- or extensively drug resistant M. tb st ...

Elsevier2010

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