Exploring fluorinated heptose phosphate analogues as inhibitors of HldA and HldE, key enzymes in the biosynthesis of lipopolysaccharide.

The growing threat of bacterial resistance to antibiotics has led to the rise of anti-virulence strategies as a promising approach. These strategies aim to disarm bacterial pathogens and improve their clearance by the host immune system. Lipopolysaccharide, a key virulence factor in Gram-negative bacteria, has been identified as a potential target for anti-virulence agents.

A morpheein equilibrium regulates catalysis in phosphoserine phosphatase SerB2 from Mycobacterium tuberculosis.

Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is of interest as a new antituberculosis target due to its essential metabolic role in L-serine biosynthesis and effector functions in infected cells. Previous works indicated that MtSerB2 is regulated through an oligomeric transition induced by L-Ser that could serve as a basis for the design of selective allosteric inhibitors. However, the mechanism underlying this transition remains highly elusive due to the lack of experimental structural data.

Human indoleamine-2,3-dioxygenase 2 cofactor lability and low substrate affinity explained by homology modeling, molecular dynamics and molecular docking.

The human indoleamine-2,3-dioxygenase 2 (hIDO2) protein is growing of interest as it is increasingly implicated in multiple diseases (cancer, autoimmune diseases, COVID-19). However, it is only poorly reported in the literature. Its mode of action remains unknown because it does not seem to catalyze the reaction for which it is attributed: the degradation of the L-Tryptophan into N-formyl-kynurenine.

Targeting the phosphoserine phosphatase MtSerB2 for tuberculosis drug discovery, an hybrid knowledge based /fragment based approach.

Tuberculosis is currently still one of the leading causes of death from a treatable pathogen. The proportion of cases of resistance to common antibiotics is frequently increasing and the development of new drugs with new therapeutic targets is becoming necessary. The Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is an interesting enzyme to target in drug design because of its ability to allow immune evasion of the bacteria.

Structural study of bioisosteric derivatives of 5-(1-indol-3-yl)-benzotriazole and their ability to form chalcogen bonds.

Recently, inter-est in the isosteric replacement of a nitro-gen atom to selenium, sulfur or oxygen atoms has been highlighted in the design of potential inhibitors for cancer research. In this context, the structures of 5-(1-indol-3-yl)-2,1,3-benzotriazole derivatives [5-(1-indol-3-yl)-2,1,3-benzo-thia-diazole (bS, CHNS) and 5-(1-indol-3-yl)-2,1,3-benzoxa-diazole (bO, CHNO)], as well as a synthesis inter-mediate of the selenated bioisostere [5-[1-(benzensulfon-yl)-1-indol-3-yl]-2,1,3-benzoselena-diazole (p-bSe, CHNOSSe)] were determined using single-crystal X-ray diffraction (SCXRD) analyses. Despite being analogues, different crystal packing, torsion angles and supra-molecular features were observed, depending on the substitution of the central atoms of the benzotriazole.

Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine 2,3-dioxygenase 1.

Indoleamine 2,3-dioxygenase 1 has sparked interest as an immunotherapeutic target in cancer research. Its structure includes a loop, named the JK-loop, that controls the orientation of the substrate or inhibitor within the active site. However, little has been reported about the crystal structure of this loop.

Biochemical characterization of phosphoserine phosphatase SerB2 from Mycobacterium marinum.

SerB2 is an essential phosphoserine phosphatase (PSP) that has been shown to be involved in Mycobacterium tuberculosis (Mtb) immune evasion mechanisms, and a drug target for the development of new antitubercular agents. A highly similar (91.0%) orthologous enzyme exists in the surrogate organism Mycobacterium marinum (Mma) and could have acquired similar properties.

Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Phosphoserine Phosphatase.

is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen's serine pathway, it appears to be involved in immune evasion mechanisms.

Crystal structures and snapshots along the reaction pathway of human phosphoserine phosphatase.

The equilibrium between phosphorylation and dephosphorylation is one of the most important processes that takes place in living cells. Human phosphoserine phosphatase (hPSP) is a key enzyme in the production of serine by the dephosphorylation of phospho-L-serine. It is directly involved in the biosynthesis of other important metabolites such as glycine and D-serine (a neuromodulator).

Targeting the Serine Pathway: A Promising Approach against Tuberculosis?

Tuberculosis is still the leading cause of death by a single infectious agent. Effective chemotherapy has been used and improved since the 1950s, but strains resistant to this therapy and most antibacterial drugs on the market are emerging. Only 10 new drugs are in clinical trials, and two of them have already demonstrated resistance.