Biochemistry

Tryptophan (Trp) metabolism follows three main branches: the kynurenine (KP), serotonin, and indole (IP) pathways. These pathways generate bioactive metabolites that regulate immune responses, redox balance, neurotransmission, metabolic homeostasis, inflammation, and circadian rhythms. A common theme across these pathways is the activation of the aryl hydrocarbon receptor (AhR). Several metabolit…

Understanding how dioxygen accesses buried catalytic centers in metalloenzymes is critical for elucidating enzymatic kinetics and guiding strategies to modulate catalytic activity. Here, we report over 20 μs of classical molecular dynamics simulations of the PHD2 oxygenase, a metalloenzyme regulating hypoxia signaling via HIF-1α hydroxylation. Our extended simulations reveal multiple dynamic diox…

Adrenal glands are one of the pivotal glands of the human endocrine system. Recently, the extracellular matrix (ECM) of the adrenal capsule and cortex was explored in two fractions: outer fraction (OF) and inner fraction (IF). A significant variation in the ECM proteins' levels, including collagens, was documented. Collagen undergoes a plethora of post-translational modifications (PTMs), exhibiti…

Fidelity of DNA polymerases, defined as their ability to incorporate a correct dNMP opposite an undamaged template nucleotide, is a key factor in ensuring genome stability. Many DNA polymerases have been extensively investigated to understand the structural and biochemical basis of their fidelity. However, the great majority of these studies employed simple primer-template substrates, disregardin…

Optical, microplate reader-based assays are a standard tool for the initial biochemical analysis of SARS-CoV-2 main protease (M^pro) inhibitor candidates. Such assays monitor M^pro-catalyzed substrate proteolysis in order to investigate the kinetic impact of inhibitors under examination on the catalytic reaction. This review outlines the numerous intricate considerations invol…

Microproteins are defined as polypeptides of 100-150 or fewer amino acids. With the integrated application of ribosome profiling (Ribo-Seq), mass spectrometry, and bioinformatic approaches, more microproteins have been identified as being encoded by small open reading frames (sORFs). The majority of microproteins are evolutionarily young and may represent species-specific events. This review high…

In eukaryotes, genomic DNA is packaged into hierarchical higher-order chromatin structures. Regulation of this organization is essential for the faithful maintenance and controlled expression of genetic information. Assembly of the nucleosome─the fundamental unit of chromatin─depends on a tightly coordinated network of histone chaperones that escort histones from their initial synthesis through m…

Bacterial membrane proteins make up ∼ 30% of the prokaryotic genome and play key roles in infection and virulence. Membrane protein chemistry has advanced in recent years, including purification strategies that mimic nativelike lipid environments, such as lipid nanoparticles, amphipols, and nanodiscs. The use of styrene maleic acid copolymers (SMALPs) to form a lipid nanoparticle has become incre…

Endocellulases are central to cellulose deconstruction but are commonly viewed as stochastic catalysts whose product distributions are difficult to control. Here, we report a loop encoded mechanism that governs cleavage-site selection in GH5 endocellulases. By comparing two closely related enzymes with distinct product profiles, we show that a short loop near the binding cleft determines substrat…

Bacterial surface polysaccharides are versatile structures that provide specificity to the behavior and interactions of a given bacterial strain. One surface polysaccharide displayed on the organism <i>Bacteroides fragilis</i>, Capsular Polysaccharide A, has been implicated as a potential therapeutic for autoimmune disorders. This polymer is composed of repeating units of the tetrasaccharide 2-ac…

Obesity and its associated metabolic syndrome present significant therapeutic challenges, with current pharmacological interventions often falling short of replicating the multifaceted benefits of bariatric surgery. Recent advances in incretin-based therapies, particularly GLP-1 and GIP coagonists, have demonstrated substantial improvements in glycemic control and weight management, yet residual …

The L-type voltage-gated Ca²⁺ channel (Ca_V1.2) controls gene expression, cardiac function, and neuronal excitability. Mutations in Ca_V1.2 that disrupt channel function are implicated in cardiac arrhythmias, vascular dysfunction, Timothy Syndrome, and epilepsy. Calcium-binding protein 1 (CaBP1) binds to the IQ-motif in Ca_V1.2 (residues 1640-1665), blocks…

Nonpathogenic cellular prion protein (PrP^C) is expressed by neurons and other cells, regulating neurite outgrowth, cell survival, myelin maintenance, and immunity, yet the PrP^C-protein interaction network and signaling pathways that underlie PrP^C function remain incompletely understood. PrP^C is glycophosphatidylinositol-anchored in lipid rafts and repor…

Supramolecular β-sheet peptide nanomaterials are of critical interest due to their relevance in amyloid disorders and are increasingly valued for applications in regenerative medicine, tissue engineering, and antimicrobial design. Amphipathic peptides, particularly those with alternating hydrophobic and hydrophilic residues, readily form amyloid-like pleated β-sheet fibrils. It has been demonstra…

Endonuclease G (EndoG) is a conserved endonuclease implicated in mitochondrial DNA (mtDNA) replication, maintenance of mtDNA integrity under oxidative stress, and the removal of nuclear and paternal mtDNA during apoptosis and early embryogenesis. Despite its biological significance, the substrates targeted by EndoG and its cleavage preferences remain unclear. Here, we characterize human EndoG (hE…

Recently, a growing number of novel types of regulated cell death have been reported, including pyroptosis, necroptosis, and ferroptosis, among others. These types of cell death play crucial roles in a wide array of physiological functions such as metabolism, tissue injury and repair, chronic disease progression, and immune protection. However, specifically targeting cell death pathways for thera…

<i>O</i>-GlcNAcylation is a dynamic posttranslational modification regulated by the enzymes <i>O</i>-GlcNAc transferase (OGT) and <i>O</i>-GlcNAc hydrolase (OGA). It involves the attachment of <i>N</i>-acetylglucosamine to serine or threonine residues of proteins in the cytosol, nucleus, and mitochondria. As a dynamic and abundant modification, <i>O</i>-GlcNAcylation functions as a sensor of the …

A vast library of bioactive peptides provides a versatile toolkit for engineering biological functionality into materials. This peptide repertoire encompasses a broad range of bioactivities, including cell adhesion, protease lability, signaling activation, and immunomodulation. As a result, these peptides have been widely used in biomaterial design to instruct cell behavior and control biological…

Bioorganic chemists are inspired by natural biopolymers to design peptidomimetic oligomers that can exhibit sequence-structure-function relationships. Biomimetic polymers can be synthesized to incorporate a specific sequence of nonbiological monomer units using a variety of iterative solution-phase or solid-phase reaction schemes. These protocols generally provide access to a vast diversity of ol…