Severe Combined Immunodeficiency from a Homozygous DNA Ligase 1 Mutant with Reduced Catalytic Activity but Increased Ligation Fidelity.

A cell's ability to survive and to evade cancer is contingent on its ability to retain genomic integrity, which can be seriously compromised when nucleic acid phosphodiester bonds are disrupted. DNA Ligase 1 (LIG1) plays a key role in genome maintenance by sealing single-stranded nicks that are produced during DNA replication and repair. Autosomal recessive mutations in a limited number of individuals have been previously described for this gene.

Using In Silico Molecular Docking to Explain Differences in Receptor Binding Behavior of HHC and THCV Isomers: Revealing New Binding Modes.

Even slight structural differences between phytocannabinoid isomers are usually enough to cause a change in their biological properties. In this study, we used in vitro CB1 agonism/antagonism assays to compare the receptor binding functionality of THCV (tetrahydrocannabivarin) and HHC (hexahydrocannabinol) isomers and applied molecular docking to provide an explanation for the difference in the activities. No CB1 agonism was observed for ∆9- and ∆8-THCV.

The formation of HuR/YB1 complex is required for the stabilization of target mRNA to promote myogenesis.

mRNA stability is the mechanism by which cells protect transcripts allowing their expression to execute various functions that affect cell metabolism and fate. It is well-established that RNA binding proteins (RBPs) such as HuR use their ability to stabilize mRNA targets to modulate vital processes such as muscle fiber formation (myogenesis). However, the machinery and the mechanisms regulating mRNA stabilization are still elusive.

Modeling of the Electrostatic Interaction and Catalytic Activity of [NiFe] Hydrogenases on a Planar Electrode.

Hydrogenases are a group of enzymes that have caught the interest of researchers in renewable energies, due to their ability to catalyze the redox reaction of hydrogen. The exploitation of hydrogenases in electrochemical devices requires their immobilization on the surface of suitable electrodes, such as graphite. The orientation of the enzyme on the electrode is important to ensure a good flux of electrons to the catalytic center, through an array of iron-sulfur clusters.

Binding of a Soluble -Tetraarylporphyrin to Human Galectin-7 Induces Oligomerization and Modulates Its Pro-Apoptotic Activity.

The selective targeting of protein-protein interactions remains a significant determinant for the proper modulation and regulation of cell apoptosis. Prototypic galectins such as human galectin-7 (GAL-7) are characterized by their ability to form homodimers that control the molecular fate of a cell by mediating subtle yet critical glycan-dependent interactions between pro- and anti-apoptotic molecular partners. Altering the structural architecture of GAL-7 can therefore result in resistance to apoptosis in various human cancer cells, further illustrating its importance in cell survival.

Genome sequencing and functional characterization of a Dictyopanus pusillus fungal enzymatic extract offers a promising alternative for lignocellulose pretreatment of oil palm residues.

The pretreatment of biomass remains a critical requirement for bio-renewable fuel production from lignocellulose. Although current processes primarily involve chemical and physical approaches, the biological breakdown of lignin using enzymes and microorganisms is quickly becoming an interesting eco-friendly alternative to classical processes. As a result, bioprospection of wild fungi from naturally occurring lignin-rich sources remains a suitable method to uncover and isolate new species exhibiting ligninolytic activity.

Cationic Ru Cyclopentadienyl Complexes with Antifungal Activity against Several Candida Species.

Fungal infections, including those caused by antifungal-resistant Candida, are a very challenging health problem worldwide. Whereas different ruthenium complexes were previously studied for their anti-Candida potential, Ru-cyclopentadienyl complexes were overlooked. Here, we report an antifungal activity assessment of three Ru-cyclopentadienyl complexes with some insights into their potential mode of action.

Artificial iron hydrogenase made by covalent grafting of Knölker's complex into xylanase: Application in asymmetric hydrogenation of an aryl ketone in water.

We report a new artificial hydrogenase made by covalent anchoring of the iron Knölker's complex to a xylanase S212C variant. This artificial metalloenzyme was found to be able to catalyze efficiently the transfer hydrogenation of the benchmark substrate trifluoroacetophenone by sodium formate in water, yielding the corresponding secondary alcohol as a racemic. The reaction proceeded more than threefold faster with the XlnS212CK biohybrid than with the Knölker's complex alone.

Dissecting the evolvability landscape of the CalB active site toward aromatic substrates.

A key event in the directed evolution of enzymes is the systematic use of mutagenesis and selection, a process that can give rise to mutant libraries containing millions of protein variants. To this day, the functional analysis and identification of active variants among such high numbers of mutational possibilities is not a trivial task. Here, we describe a combinatorial semi-rational approach to partly overcome this challenge and help design smaller and smarter mutant libraries.

Serotonin and serotonin reuptake inhibitors alter placental aromatase.

Serotonin reuptake inhibitors (SRIs) are currently the main molecules prescribed to pregnant women that suffer from depression. Placental cells are exposed to SRIs via maternal blood, and we have previously shown that SRIs alter feto-placental steroidogenesis in an in vitro co-culture model. More specifically, serotonin (5-HT) regulates the estrogen biosynthetic enzyme aromatase (cytochrome P450 19; CYP19), which is disrupted by fluoxetine and its active metabolite norfluoxetine in BeWo choriocarcinoma cells.

Importance of the β5-β6 Loop for the Structure, Catalytic Efficiency, and Stability of Carbapenem-Hydrolyzing Class D β-Lactamase Subfamily OXA-143.

The class D β-lactamase OXA-143 has been described as an efficient penicillinase, oxacillinase, and carbapenemase. The D224A variant, known as OXA-231, was described in 2012 as exhibiting less activity toward imipenem and increased oxacillinase activity. Additionally, the P227S mutation was reported as a case of convergent evolution for homologous enzymes.

Semi-rational evolution of the 3-(3-hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA to improve rhamnolipid production in Pseudomonas aeruginosa and Burkholderia glumae.

The 3-(3-hydroxyalkanoyloxy)alkanoate (HAA) synthase RhlA is an essential enzyme involved in the biosynthesis of HAAs in Pseudomonas and Burkholderia species. RhlA modulates the aliphatic chain length in rhamnolipids, conferring distinct physicochemical properties to these biosurfactants exhibiting promising industrial and pharmaceutical value. A detailed molecular understanding of substrate specificity and catalytic performance in RhlA could offer protein engineering tools to develop designer variants involved in the synthesis of novel rhamnolipid mixtures for tailored eco-friendly products.

A comparative metagenomic and spectroscopic analysis of soils from an international point of entry between the US and Mexico.

The Paso del Norte region is characterized by its dynamic industries and active agriculture. Throughout the years, urban and agricultural soils from this region have been exposed to xenobiotics, heavy metals, and excess of hydrocarbons. In this study, samples of urban [domestic workshops (DW)] and agricultural-intended (AI) soils from different sites of Ciudad Juárez, Mexico were evaluated for their fertility, element content, and microbial diversity.

Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks.

Phosphotyrosine (pTyr) signaling has evolved into a key cell-to-cell communication system. Activated receptor tyrosine kinases (RTKs) initiate several pTyr-dependent signaling networks by creating the docking sites required for the assembly of protein complexes. However, the mechanisms leading to network disassembly and its consequence on signal transduction remain essentially unknown.

Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa.

Bacteria have evolved multiple strategies for causing infections that include producing virulence factors, undertaking motility, developing biofilms, and invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) tightly regulates the expression of multiple virulence factors in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS could lead to health benefits.

Genetic engineering of the phosphocarrier protein NPr of the Escherichia coli phosphotransferase system selectively improves sugar uptake activity.

The Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system (PTS) in prokaryotes mediates the uptake and phosphorylation of its numerous substrates through a phosphoryl transfer chain where a phosphoryl transfer protein, HPr, transfers its phosphoryl group to any of several sugar-specific Enzyme IIA proteins in preparation for sugar transport. A phosphoryl transfer protein of the PTS, NPr, homologous to HPr, functions to regulate nitrogen metabolism and shows virtually no enzymatic cross-reactivity with HPr. Here we describe the genetic engineering of a "chimeric" HPr/NPr protein, termed CPr14 because 14 amino acid residues of the interface were replaced.