Systematic analysis of structural disorder in the minimal proteome of .

(Mpn, class ) is both an important human pathogen and a model organism. We performed a proteome-wide investigation of intrinsically disordered regions (IDRs) in Mpn. Compared to other bacteria, a considerable fraction of the Mpn proteome (17%) is embedded in IDRs, which are abundant in membrane, non-essential proteins, as well as in proteins that mediate cytoadherence and virulence.

Comparative analysis of Polyethylene-Degrading Laccases: Redox Properties and Enzyme-Polyethylene Interaction Mechanism.

Laccases that oxidize low-density polyethylene (LDPE) represent a promising strategy for bioremediation purposes. To rationalize or optimize their PE-oxidative activity, two fundamental factors must be considered: the enzyme's redox potential and its binding affinity/mode towards LDPE. Indeed, a stable laccase-PE complex may facilitate a thermodynamically unfavorable electron transfer, even without redox mediators.

Structural insights into temperature-dependent dynamics of METPsc1, a miniaturized electron-transfer protein.

The design of protein-metal complexes is rapidly advancing, with applications spanning catalysis, sensing, and bioremediation. We report a comprehensive investigation of METPsc1, a Miniaturized Electron Transfer Protein, in complex with cadmium. This study elucidates the impact of metal coordination on protein folding and structural dynamics across temperatures from 100 K to 300 K.

A conserved acidic residue drives thyroxine synthesis within thyroglobulin and other protein precursors.

Thyroxine, the main hormone product of the thyroid, is produced at multiple sites within its protein precursor thyroglobulin. Each site consists of two tyrosine residues which undergo iodination and coupling, resulting in the synthesis of thyroxine at the acceptor tyrosine, where the hormone synthesis is later completed by proteolysis. Within the structurally resolved sites, the role of an essential conserved acidic residue preceding the acceptor remains elusive.

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features.

Mechanism of non-phenolic substrate oxidation by the fungal laccase Type 1 copper site from : the case of benzo[]pyrene and anthracene.

Laccases (EC 1.10.3.

C-Cl Bond Activation at Rotated vs Unrotated Dinuclear Site Related to [FeFe]-Hydrogenases.

The novel dinuclear complex related to the [FeFe]-hydrogenases active site, [Fe(μ-pdt)(κ-dmpe)(CO)] (), is highly reactive toward chlorinated compounds CHCl ( = 1, 2) affording selectively terminal or bridging chloro diiron isomers through a C-Cl bond activation. DFT calculations suggest a cooperative mechanism involving a formal concerted regioselective chloronium transfer depending on the unrotated or rotated conformation of two isomers of .

Synthesis, Spectroscopy, and Structure of [FeRu(μ-dithiolate)(CN)(CO)].

The salt [K(18-crown-6)][Ru(CN)(CO)] ([K(18-crown-6)][]) was generated by the reaction of Ru(CH)(CO) with [K(18-crown-6)]CN. An initial thermal reaction gives [Ru(CN)(CO)], which, upon ultraviolet (UV) irradiation, reacts with a second equiv of CN. Protonation of [] gave [HRu(CN)(CO)] ([H]), which was isolated as a single isomer with mutually trans cyanide ligands.

Assessing the Performance of Non-Equilibrium Thermodynamic Integration in Flavodoxin Redox Potential Estimation.

Flavodoxins are enzymes that contain the redox-active flavin mononucleotide (FMN) cofactor and play a crucial role in numerous biological processes, including energy conversion and electron transfer. Since the redox characteristics of flavodoxins are significantly impacted by the molecular environment of the FMN cofactor, the evaluation of the interplay between the redox properties of the flavin cofactor and its molecular surroundings in flavoproteins is a critical area of investigation for both fundamental research and technological advancements, as the electrochemical tuning of flavoproteins is necessary for optimal interaction with redox acceptor or donor molecules. In order to facilitate the rational design of biomolecular devices, it is imperative to have access to computational tools that can accurately predict the redox potential of both natural and artificial flavoproteins.

Selective events at individual sites underlie the evolution of monkeypox virus clades.

In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (Clades I and II) that differ in virulence and host associations. Clade IIb is closely related to the B.1 lineage, which is dominating a worldwide outbreak initiated in 2022.

Activation of the N molecule by means of low-valence complexes of calcium and magnesium.

Nitrogen gas is a highly inert molecule and its activation under mild conditions represents a crucial goal in current research. In a recent study, the discovery of low-valence Ca(I) compounds capable of coordinating and reducing N was reported [B. Rösch, T.

Recent Theoretical Insights into the Oxidative Degradation of Biopolymers and Plastics by Metalloenzymes.

Molecular modeling techniques have become indispensable in many fields of molecular sciences in which the details related to mechanisms and reactivity need to be studied at an atomistic level. This review article provides a collection of computational modeling works on a topic of enormous interest and urgent relevance: the properties of metalloenzymes involved in the degradation and valorization of natural biopolymers and synthetic plastics on the basis of both circular biofuel production and bioremediation strategies. In particular, we will focus on lytic polysaccharide monooxygenase, laccases, and various heme peroxidases involved in the processing of polysaccharides, lignins, rubbers, and some synthetic polymers.

Normal vs. Inverted Ordering of Reduction Potentials in [FeFe]-Hydrogenases Biomimetics: Effect of the Dithiolate Bulk.

Three hexacarbonyl diiron dithiolate complexes [Fe (CO) (μ-(SCH ) X)] with different substituted bridgeheads (X=CH , CEt , CBn (Bn=CH C H )), have been studied under the same experimental conditions by cyclic voltammetry in dichloromethane [NBu ][PF ] 0.2 M. DFT calculations were performed to rationalize the mechanism of reduction of these compounds.

Conjugation of gold nanoparticles with multidentate surfactants for enhanced stability and biological properties.

This work originated from the need to functionalize surfactant-coated inorganic nanoparticles for biomedical applications, a process that is limited by excess unbound surfactant. These limitations are connected to the bioconjugation of targeting molecules that are often in equilibrium between the free aliquot in solution and that which binds the surface of the nanoparticles. The excess in solution can play a role in the biocompatability and of the final nanoparticles stock.

A De Novo-Designed Type 3 Copper Protein Tunes Catechol Substrate Recognition and Reactivity.

De novo metalloprotein design is a remarkable approach to shape protein scaffolds toward specific functions. Here, we report the design and characterization of Due Rame 1 (DR1), a de novo designed protein housing a di-copper site and mimicking the Type 3 (T3) copper-containing polyphenol oxidases (PPOs). To achieve this goal, we hierarchically designed the first and the second di-metal coordination spheres to engineer the di-copper site into a simple four-helix bundle scaffold.

Exome Sequencing in an ADSHE Family: VUS Identification and Limits.

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is the familial form of a focal epilepsy characterized by hyperkinetic focal seizures, mainly arising during non-rapid eye movements (NREM) sleep. Mutations associated with ADSHE account for a small proportion of the genetically determined cases, suggesting the existence of other disease-causing genes. Here, we reported the results obtained by performing trio-based whole-exome sequencing (WES) in an Italian family showing ADSHE and investigated the structural impact of putative variants by in silico modeling analysis.

Revisiting Viewing Graph Solvability: An Effective Approach Based on Cycle Consistency.

In the structure from motion, the viewing graph is a graph where the vertices correspond to cameras (or images) and the edges represent the fundamental matrices. We provide a new formulation and an algorithm for determining whether a viewing graph is solvable, i.e.

Machine Learning for Efficient Prediction of Protein Redox Potential: The Flavoproteins Case.

Determining the redox potentials of protein cofactors and how they are influenced by their molecular neighborhoods is essential for basic research and many biotechnological applications, from biosensors and biocatalysis to bioremediation and bioelectronics. The laborious determination of redox potential with current experimental technologies pushes forward the need for computational approaches that can reliably predict it. Although current computational approaches based on quantum and molecular mechanics are accurate, their large computational costs hinder their usage.

Insights into Triazolylidene Ligands Behaviour at a Di-Iron Site Related to [FeFe]-Hydrogenases.

The behaviour of triazolylidene ligands coordinated at a {Fe(CO)(µ-dithiolate)} core related to the active site of [FeFe]-hydrogenases have been considered to determine whether such carbenes may act as redox electron-reservoirs, with innocent or non-innocent properties. A novel complex featuring a mesoionic carbene (MIC) [Fe(CO)(Pmpt)(µ-pdt)] (; Pmpt = 1-phenyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene; pdt = propanedithiolate) was synthesized and characterized by IR, H, C{H} NMR spectroscopies, elemental analyses, X-ray diffraction ,and cyclic voltammetry. Comparison with the spectroscopic characteristics of its analogue [Fe(CO)(Pmbt)(µ-pdt)] (; Pmbt = 1-phenyl-3-methyl-4-butyl-1,2,3-triazol-5-ylidene) showed the effect of the replacement of a n-butyl by a phenyl group in the 1,2,3-triazole heterocycle.

Geometrical influence on the non-biomimetic heterolytic splitting of H by bio-inspired [FeFe]-hydrogenase complexes: a rare example of frustrated Lewis pair based reactivity.

Despite the high levels of interest in the synthesis of bio-inspired [FeFe]-hydrogenase complexes, H oxidation, which is one specific aspect of hydrogenase enzymatic activity, is not observed for most reported complexes. To attempt H-H bond cleavage, two disubstituted diiron dithiolate complexes in the form of [Fe(μ-pdt)L(CO)] (L: PMe, dmpe) have been used to play the non-biomimetic role of a Lewis base, with frustrated Lewis pairs (FLPs) formed in the presence of B(CF) Lewis acid. These unprecedented FLPs, based on the bimetallic Lewis base partner, allow the heterolytic splitting of the H molecule, forming a protonated diiron cation and hydrido-borate anion.

Dating the Emergence of Human Endemic Coronaviruses.

Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtained similar tMRCA (time to the most recent common ancestor) estimates for the four coronaviruses, ranging from 72 (HCoV-229E) to 54 (HCoV-NL63) years ago.

Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS.

Homology-based classification of accessory proteins in coronavirus genomes uncovers extremely dynamic evolution of gene content.

Coronaviruses (CoVs) have complex genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ even among closely related viruses. Accessory proteins often play a role in the suppression of immune responses and may represent virulence factors. Despite their relevance for CoV phenotypic variability, information on accessory proteins is fragmentary.

Challenges in the Synthesis of Active Site Mimics for [NiFe]-Hydrogenases.

One of the more active areas in bioorganometallic chemistry is the preparation and reactivity studies of active site mimics of the [NiFe]-hydrogenases. One area of particular recent progress involves reactions that interconvert Ni(-X)Fe centers for X = OH, H, CO, as described by Song et al. Such reactions illustrate new ways to access intermediates related to the Ni-R and Ni-SI states of the enzyme.

Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host.

Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins.