Claude Didierjean

Precise control of peptide backbone folding through non‐covalent interactions remains a major challenge in foldamer design. In this work, we demonstrate that heteroatom substitutions program conformational switching in azole γ‐peptides by tuning intrinsic stereoelectronic effects within heterocyclic γ‐amino acids. Conformationally constrained thiazole‐ and oxazole‐based γ‐amino acids were designed to adopt conformations driven by either a C ₉ or a C ₇ intramolecular H‐bond depending on key 1,4‐X···O interactions (X = S or N). We previously showed that thiazole‐based oligomers form a well‐characterized canonical 9‐Helix. Here, permutation of the sulfur and nitrogen atoms within the heterocycle induces a stretched helical structure with alternating C ₇ ‐turns and residues in extended conformations. This unusual topology arises from competition between seven‐membered intra‐residue H‐bonds and attractive S···N electrostatic‐chalcogen interactions. Reversing this effect through an S→O substitution affords oxazole‐derived oligomers that adopt a stable 7‐Helix stabilized by a continuous seven‐membered H‐bond network in solution. These findings show that simple heteroatom permutation or substitution allows control over heterocyclic γ‐peptide folding, thereby expanding opportunities for foldamer design in molecular recognition, catalysis, and biomedical applications.

Precise control of peptide backbone folding through non‐covalent interactions remains a major challenge in foldamer design. In this work, we demonstrate that heteroatom substitutions program conformational switching in azole γ‐peptides by tuning intrinsic stereoelectronic effects within heterocyclic γ‐amino acids. Conformationally constrained thiazole‐ and oxazole‐based γ‐amino acids were designed to adopt conformations driven by either a C ₉ or a C ₇ intramolecular H‐bond depending on key 1,4‐X···O interactions (X = S or N). We previously showed that thiazole‐based oligomers form a well‐characterized canonical 9‐Helix. Here, permutation of the sulfur and nitrogen atoms within the heterocycle induces a stretched helical structure with alternating C ₇ ‐turns and residues in extended conformations. This unusual topology arises from competition between seven‐membered intra‐residue H‐bonds and attractive S···N electrostatic‐chalcogen interactions. Reversing this effect through an S→O substitution affords oxazole‐derived oligomers that adopt a stable 7‐Helix stabilized by a continuous seven‐membered H‐bond network in solution. These findings show that simple heteroatom permutation or substitution allows control over heterocyclic γ‐peptide folding, thereby expanding opportunities for foldamer design in molecular recognition, catalysis, and biomedical applications.

Glutathione transferases (GSTs) constitute a widespread superfamily of multifunctional enzymes with roles in cellular detoxification and secondary metabolism. We report that the poorly characterized Iota‐class enzymes (GSTIs) are mainly found in photosynthetic prokaryotes and eukaryotes, excluding Spermatophyta, and in a few fungi of the order Chytridiomycota. GSTIs are distinguished from other GSTs by the presence of N‐ and C‐terminal extensions of unknown function flanking the central GST domain. Focusing on the GSTI enzyme (SynGSTI1) of the model cyanobacterium Synechocystis sp. PCC 6803 ( S.6803 ), we showed that recombinant SynGSTI1 protein purified from Escherichia coli and S.6803 exhibited thiol‐transferase and dehydroascorbate reductase activities consistent with the presence of a CPYC catalytic motif in its GST domain. SynGSTI1 was found to be monomeric and to exhibit a spectrophotometric signature between 300 and 500 nm, which was attributed to a flavin mononucleotide (FMN). The C‐terminal domain of SynGSTI1 contained a conserved PRDM/L motif involved in the binding of an FMN ligand and showed a structure similar to that of the α‐subunit of phycoerythrin components of the light‐harvesting antenna of some cyanobacteria, most red algae and some cryptophytes. The deletion of the SynGSTI1 encoding gene in S.6803 (i) caused a slight decrease in the photosynthetic pigment content without impairing growth in standard photoautotrophic conditions; (ii) increased sensitivity to moderate and high light intensities; (iii) reduced glutathione levels and consistently; (iv) decreased tolerance to oxidative and metal stresses triggered by H ₂ O ₂ , diamide and cobalt. Thus, SynGSTI1 defines a unique GST subclass with critical roles in redox homeostasis and stress tolerance.

Plastic pollution has emerged as a critical environmental challenge due to the widespread accumulation of petrochemical plastics in natural ecosystems. Conventional waste management strategies, including mechanical recycling and incineration, have demonstrated limited efficiency in addressing the persistence of plastics such as polyethylene, polypropylene, polyethylene terephthalate, and polyvinyl chloride. While incineration eliminates plastic material, it does not promote circularity and may generate toxic emissions. As a sustainable alternative, microbial biodegradation involves bacteria, fungi, and actinomycetes capable of degrading synthetic polymers through enzymatic processes. This review provides a comprehensive overview of microbial degradation of major plastics such as polyethylene, polypropylene, polyethylene terephthalate, and polyvinyl chloride, highlighting key strains, degradation rates, and enzymatic mechanisms. Importantly, biodegradation research also informs the development of in situ remediation technologies and supports new recycling strategies. Advances in protein engineering and synthetic biology are discussed for enhancing degradation efficiency. However, scaling biodegradation to environmental conditions remains challenging due to variable temperature, pH, microbial competition, and potentially toxic intermediates. Despite these limitations, microbial biodegradation represents a promising ecofriendly approach to address plastic waste and promote a biobased circular economy. Future work should integrate microbial processes into existing recycling infrastructure and design robust consortia guided by omics tools.

Photosynthetic organisms have a high diversity of proteins belonging to the thioredoxin (TRX) superfamily. It comprises more than 150 proteins distributed in different families and classes, including thioredoxins, glutaredoxins, protein disulfide isomerases, thiol peroxidases, and glutathione transferases, which all share the thioredoxin structural fold. Many of them have one or two redox-active cysteines and a characteristic cis-proline at specific positions, and additional domains or secondary structures at either end or inserted into the protein core. With the aim of further describing the TRX family in plants, we have identified a set of 17 atypical TRX-like proteins from Arabidopsis, which have not been considered before despite having both a TRX fold and the CxxC/S signature typical of redox-active TRXs. In silico sequence and structure analyses revealed that they are divided into eight distinct classes with unique active-site signatures and structures, some with disulfide bond-forming protein A (DsbA) and peroxiredoxin-like folds. Their distinct subcellular localizations (plastids, mitochondria, extracellular space) and gene expression profiles suggest that these proteins are involved in diverse cellular processes, further expanding the set of proteins involved in redox regulation and/or stress adaptation. Our results reveal additional diversity in the structure and function of atypical TRXs in plants.

Bacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria. However, the functional packing and precise role of VirB8 in T4SSs biology remain undefined. Our findings elucidate the nature of VirB8 proteins as cell wall components, where they multimerize and exhibit a conserved assembly pattern, distinct from VirB8 in Gram-negative bacteria. We also demonstrate that VirB8 proteins interact with other T4SS subunits and DNA, indicating their pivotal role in the building of the DNA translocation channel across the cell wall. We lastly propose a distinct architecture for conjugative T4SSs in Gram-positive bacteria compared to their Gram-negative counterparts, possibly attributed to the differences in the cell wall structure.

This study presents a comprehensive analysis of the dimerization interfaces of fly GSTs through sequence alignment. Our investigation revealed GSTE1 as a particularly intriguing target, providing valuable insights into the variations within Delta and Epsilon GST interfaces. The X-ray structure of GSTE1 was determined, unveiling remarkable thermal stability and a distinctive dimerization interface. Utilizing circular dichroism, we assessed the thermal stability of GSTE1 and other Drosophila GSTs with resolved X-ray structures. The subsequent examination of GST dimer stability correlated with the dimerization interface supported by findings from X-ray structural analysis and thermal stability measurements. Our discussion extends to the broader context of GST dimer interfaces, offering a generalized perspective on their stability. This research enhances our understanding of the structural and thermodynamic aspects of GST dimerization, contributing valuable insights to the field.

Glutathione transferases (GST) are detoxification enzymes that conjugate glutathione to a wide array of molecules. In the honey bee Apis mellifera, AmGSTD1 is the sole member of the delta class of GSTs, with expression in antennae. Here, we structurally and biochemically characterized AmGSTD1 to elucidate its function. We showed that AmGSTD1 can efficiently catalyse the glutathione conjugation of classical GST substrates. Additionally, AmGSTD1 exhibits binding properties with a range of odorant compounds. AmGSTD1 has a peculiar interface with a structural motif we propose to call ‘sulfur sandwich’. This motif consists of a cysteine disulfide bridge sandwiched between the sulfur atoms of two methionine residues and is stabilized by CH…S hydrogen bonds and S…S sigma‐hole interactions. Thermal stability studies confirmed that this motif is important for AmGSTD1 stability and, thus, could facilitate its functions in olfaction.

Neuropilin 1 (NRP1), a cell-surface co-receptor of a number of growth factors and other signaling molecules, has long been the focus of attention due to its association with the development and the progression of several types of cancer. For example, the KDKPPR peptide has recently been combined with a photosensitizer and a contrast agent to bind NRP1 for the detection and treatment by photodynamic therapy of glioblastoma, an aggressive brain cancer. The main therapeutic target is a pocket of the fragment b1 of NRP1 (NRP1-b1), in which vascular endothelial growth factors (VEGFs) bind. In the crystal packing of native human NRP1-b1, the VEGF-binding site is obstructed by a crystallographic symmetry neighbor protein, which prevents the binding of ligands. Six charged amino acids located at the protein surface were mutated to allow the protein to form a new crystal packing. The structure of the mutated fragment b1 complexed with the KDKPPR peptide was determined by X-ray crystallography. The variant crystallized in a new crystal form with the VEGF-binding cleft exposed to the solvent and, as expected, filled by the C-terminal moiety of the peptide. The atomic interactions were analyzed using new approaches based on a multipolar electron density model. Among other things, these methods indicated the role played by Asp320 and Glu348 in the electrostatic steering of the ligand in its binding site. Molecular dynamics simulations were carried out to further analyze the peptide binding and motion of the wild-type and mutant proteins. The simulations revealed that specific loops interacting with the peptide exhibited mobility in both the unbound and bound forms.