Cytochrome P450 CYP152s catalyze decarboxylation of fatty acids to generate terminal alkenes, valuable compounds for various industries. Here, we identified, overexpressed, and characterized a new CYP152 enzyme from Lacicoccus alkaliphilus (OleTLA), and compared its biophysical and biochemical properties with the well-studied OleTJE from Jeotgalicoccus sp. 8456. Improved expression protocols gave the

Spinal cord injury (SCI) induces rapid and extensive skeletal muscle atrophy. During skeletal muscle atrophy, numerous extracellular matrix (ECM) and fibroblasts accumulate, impairing muscle function. The pro-viral Integration site for moloney murine leukaemia virus kinases-1(PIM1) is considered a positive regulator of inflammation. In our study, we found that PIM1 was overexpressed in the fibrotic

As part of the innate immune response, the host withholds metal micronutrients such as iron (Fe) from invading pathogens. To survive such Fe-limitation, the opportunistic fungal pathogen Candida albicans has evolved elaborate responses to Fe-starvation stress. One such adaptation involves secretion of flavins, yellow isoalloxazine compounds that serve important redox roles in biology. Why the organism

Cytochrome c oxidase (CcO) catalyzes oxygen (O2) reduction at the heme a3-CuB site in the transmembrane region of the enzyme. It has been proposed that the hydrophobic channel that connects the transmembrane surface of subunit III through subunit I to the heme a3-CuB site is the O2 transfer pathway. Gas molecules other than O2, including carbon dioxide (CO2) generated in the TCA cycle, should also

The survival of Mycobacterium tuberculosis relies on its ability to adapt to dynamic and hostile host environments. Amino acid decarboxylases play a crucial role in these adaptations, but their structural and mechanistic properties are not fully understood. Bioinformatic analyses revealed that these enzymes exist in three distinct forms based on their domain organization. We used cryogenic electron

The Rag GTPases play an important role in sensing amino acids and activating the target of rapamycin complex 1 (TORC1), a master regulator of cell metabolism. Previously, we have shown that GDP-bound RagA stimulates lysosome acidification and autophagic degradation, which are essential for young egg chamber survival under starvation in Drosophila. However, the underlying mechanism is unclear. Here

In many proteinopathies, the relative conformations of amyloid fibrils versus smaller oligomers remain unclear. Most tissue-derived isolates of infectious prion protein (PrP) prions are predominantly fibrillar. A few studies have asserted that prion amyloid fibrils efficiently disassemble into dimeric to tetrameric "elemental bricks" under certain detergent or chaotropic conditions, but our companion

Humanin is an endogenous human peptide with cytoprotective effects including inhibition of apoptosis via interaction with BCL-2 proteins such as BAX. The therapeutic benefits of HN have been well-documented, and administering humanin and related endogenous human peptides for treatment of disease, aging, and enhancement of athletic performance is becoming more widespread. However, very little is known

Acylated domains (AD), like that of the Bordetella pertussis adenylate cyclase toxin (CyaA), are structures found in all pore-forming toxins from the family of Repeat-in-ToXin (RTX) proteins. These AD segments are fatty-acylated on ε-amino groups of conserved lysine residues, such as the K860 and K983 residues of CyaA. The ε-amide linked acyl chains are essential for toxin activity and promote irreversible

The unc-51-like kinase complex (ULK1C) and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) are the key regulators of macroautophagy initiation. Understanding the assembly and coordination of these two complexes is essential for deciphering their cellular regulation and targeting them for therapeutic enhancement. This review highlights recent advances in our understanding of the structural

Bacterial type II toxin-antitoxin (TA) systems exhibit high specificity within each pair to ensure precise recognition of the toxin by its cognate antitoxin to inhibit toxicity of the free toxin. Despite high structural similarity among some TAs, crosstalk between non-cognate TA pairs is rare. To determine how the E. coli RelB antitoxin suppresses its cognate RelE toxin, we engineered C-terminal truncations

The intracellular O-linked N-acetylglucosamine (O-GlcNAc) modification is known to be enriched in the nucleus and on chromatin, but many of its chromatin targets remain to be identified. Herein we demonstrate the O-GlcNAcylation of YEATS Domain Containing 2 (YEATS2), a subunit of the chromatin Ada-two-A-containing (ATAC) complex and a reader of histone H3K27ac. We show that YEATS2 interacts with the

Cisplatin-based chemotherapy is a conventional therapy for muscle-invasive bladder cancer (BC); However, its efficacy is often limited by the emergence of resistance to cisplatin. Yes-associated protein (YAP) and β-catenin are involved in this resistance, yet their upstream regulators are not well defined. This study investigates the role of TFAP2C in regulating YAP expression and its impact on cisplatin

Rather than inhibiting copper entry when grown on high Cu, yeast cells import excessive Cu while simultaneously increasing expression of metallothionein CUP1 which then sequesters the excess Cu. An ordinary-differential-equations-based kinetic model was developed to investigate this unusual behavior. The assumed reaction network included 25 reactions and 10 components in the cytosol of yeast cells

Plants have evolved xylanase inhibitor proteins as part of their defense mechanisms against phytopathogens. The rice xylanase inhibitor protein (OsXIP) is structurally similar to GH18 chitinase and homologous to wheat XIP-type inhibitor (XIP-I), which inhibits both GH10 and GH11 xylanases. Various inhibition and interaction analyses showed that OsXIP competitively inhibits the hydrolytic activity of

Here we investigate the thermodynamic driving force of internal electron transfer (ET) of pyruvate:ferredoxin oxidoreductases (PFORs), by comparing the redox properties of a series of PFORs from Chlorobaculum tepidum (Ct), Magnetococcus marinus (Mm), Methanosarccina acetivorans (Ma), as well as revisiting the single historical precedent, the enzyme from Desulfovibrio africanus. These enzymes require

LPS is essential in most Gram-negative bacteria, but mutants of several species have been isolated that can survive in its absence. Caulobacter crescentus viability in the absence of LPS is partially dependent on the anionic sphingolipid ceramide diphosphoglycerate (CPG2). Genetic analyses showed that ccna_01210, which encodes a nucleotidyltransferase, is required for CPG2 production. Using purified

The collagen IV scaffold serves as a fundamental structural unit of the basement membrane (BM). Understanding its structure, assembly, and function is essential for tissue engineering, design of organoid models, and developing therapies for diseases such as Alport syndrome, Gould syndrome, psoriasis, eye abnormalities, hearing loss, and others where collagen IV is required for structural integrity

Atherosclerosis develops at predictable sites in the vasculature where branch points and curvatures create non-laminar disturbed flow. This disturbed flow causes vascular inflammation by increased endothelial cell (EC) barrier permeability and the expression of inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1). Vascular endothelial growth factor receptor 2 (VEGFR2) regulates flow-induced

KTX-1001 is a small molecule inhibitor of MMSET in early clinical development for multiple myeloma. It was identified as a potent and selective inhibitor of MMSET (also known as NSD2) using a high throughput biochemical assay with LC/MS-MS detection of SAH production as the endpoint. Subsequent evaluation of the binding of KTX-1001 to its target was conducted using surface plasmon resonance (SPR) to

Colchicine (Col) is a traditional herbal medicine derived from the plant Colchicum autumnale. With the property of anti-inflammation, Col has been demonstrated certain therapeutic effects in cardiovascular diseases (CVDs). Vascular calcification is positively related to the morbidity and mortality of CVDs. However, the specific cardiovascular conditions for which Col is effective remain unclear, particularly

Protein−carbohydrate binding plays an essential role in biological processes including cellular recognition and immune signaling. However, glycans are hydrophilic with limited hydrophobic surfaces, a challenge for selective recognition by proteins. CH–π stacking interactions are pervasive in protein-carbohydrate binding sites and have emerged as critical drivers of protein–carbohydrate recognition

The catalytic cycle of cytochrome P450 (P450) enzymes involves ferric peroxide anion (Fe3+O2¯, Compound 0) and perferryl oxygen (FeO3+, Compound I) intermediates. Compound I is generally viewed as responsible for most P450-catalyzed oxidations, but Compound 0 has been implicated in the oxidation of some carbonyl compounds, particularly deformylation reactions. We considered the hypothesis that Compound

Neurotransmitter release is a complex process involving tightly controlled co-factors and protein-protein interactions. G protein coupled receptors negatively regulate exocytosis via the interaction of G-protein βγ (Gβγ) heterodimers with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. The neuronal ternary SNARE complex comprises synaptosomal-associated protein-25

Leucine Rich Repeat Kinase 2 (LRRK2) has gone, in a little over two decades, from a novel gene linked to cases of Parkinson’s Disease (PD) in one family to being the main actionable target for PD therapeutics, with several clinical trials targeting it currently underway. While much remains to be understood about LRRK2—including, chiefly, why its increased activity is linked to PD—much has also been