Molecular pathogenesis of tumorigenesis caused by succinate dehydrogenase defect.

Succinate dehydrogenase (SDH), also named as complex II or succinate:quinone oxidoreductases (SQR) is a critical enzyme in bioenergetics and metabolism. This is because the enzyme is located at the intersection of oxidative phosphorylation and tricarboxylic acid cycle (TCA); the two major pathways involved in generating energy within cells. SDH is composed of 4 subunits and is assembled through a multi-step process with the aid of assembly factors.

Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function.

Succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), the two primary metabolic pathways for generating ATP. Impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. SDH function is tailored to meet the energy demands in different cell types.

The anti-fungal β-sitosterol targets the yeast oxysterol-binding protein Osh4.

Background: β-Sitosterol is a plant metabolite with a broad range of anti-fungal activity, however, this compound is not toxic against a few fungal species. The target of β-sitosterol and the nature of its selective toxicity are not yet clear. Using a yeast model system and taking advantage of molecular biology and computational approaches, we identify the target and explain why β-sitosterol is not toxic against some fungal pathogens.

The assembly of succinate dehydrogenase: a key enzyme in bioenergetics.

Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. This enzyme has medical significance as there is a broad range of human diseases from cancers to neurodegeneration related to SDH malfunction.

CO Cycloaddition to Epoxides by using M-DABCO Metal-Organic Frameworks and the Influence of the Synthetic Method on Catalytic Reactivity.

A series of high-quality M(BDC)(DABCO) metal-organic frameworks (abbreviated as M-DABCO; M=Zn, Co, Ni, Cu; BDC=1,4-benzene dicarboxylate; DABCO=1,4-diazabicyclo[2.2.2]octane), were synthesized by using a solvothermal (SV) method, and their catalytic activity for the cycloaddition of CO to epoxides in the absence of a co-catalyst or solvent was demonstrated.

4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Chemical Biology to Agrochemicals.

The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.

Yeast-based assays for detecting protein-protein/drug interactions and their inhibitors.

Understanding cellular processes at molecular levels in health and disease requires the knowledge of protein-protein interactions (PPIs). In line with this, identification of PPIs at genome-wide scale is highly valuable to understand how different cellular pathways are interconnected, and it eventually facilitates designing effective drugs against certain PPIs. Furthermore, investigating PPIs at a small laboratory scale for deciphering certain biochemical pathways has been demanded for years.

Discovery of a butyrylcholinesterase-specific probe via a structure-based design strategy.

We report herein the structure-based design and application of a fluorogenic molecular probe (BChE-FP) specific to butyrylcholinesterase (BChE). This probe was rationally designed by mimicking the native substrate and optimized stepwise by manipulating the steric feature and the reactivity of the designed probe targeting the structural difference of the active pockets of BChE and AChE. The refined probe, BChE-FP, exhibits high specificity toward BChE compared to AChE, producing about 275-fold greater fluorescence enhancement upon the catalysis by BChE.

Actin, Membrane Trafficking and the Control of Prion Induction, Propagation and Transmission in Yeast.

The model eukaryotic yeast Saccharomyces cerevisiae has proven a useful model system in which prion biogenesis and elimination are studied. Several yeast prions exist in budding yeast and a number of studies now suggest that these alternate protein conformations may play important roles in the cell. During the last few years cellular factors affecting prion induction, propagation and elimination have been identified.

Yeast Model of Amyloid-β and Tau Aggregation in Alzheimer's Disease.

The amyloid-β peptide (Aβ) and the phosphorylated protein tau have been widely implicated in Alzheimer's disease and are the focus of most research. Both agents have been extensively studied in mammalian cell culture and in animal studies, but new research is focusing on yeast models. Yeast are eukaryotes, just like us, and are amenable to effects and expression of Aβ and tau and appear able to 'report' with considerable relevance on the effects of these biomolecules.

Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI(+)] prion but not for prion propagation.

The continued propagation of the yeast [PSI(+)] prion requires the molecular chaperone Hsp104 yet in cells engineered to overexpress Hsp104; prion propagation is impaired leading to the rapid appearance of prion-free [psi(-)] cells. The underlying mechanism of prion loss in such cells is unknown but is assumed to be due to the complete dissolution of the prion aggregates by the ATP-dependent disaggregase activity of this chaperone. To further explore the mechanism, we have sought to identify cellular factors required for prion loss in such cells.