Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many proteins form amyloid-like fibrils in vitro under partially or highly unfolding conditions. Recently, we showed that the residual structure in highly unfolded state is closely related to amyloid fibril formation in hen lysozyme. Thus, to better understand the role of the residual structure on amyloid fibril formation, we focused on AL amyloidosis, which results from the extracellular deposition of monoclonal immunoglobulin light-chain variable domains (V(L)s) as insoluble fibrils. We examined the relationship between the residual structure and amyloid fibril formation on three lambda6 recombinant V(L) (rVlambda6) proteins, wild type, Jto, and Wil. Although rVlambda6 proteins are highly unfolded in pH 2, (15)N NMR transverse relaxation experiments revealed nonrandom structures in regions, which include some hydrophobic residues and a single disulfide bond, indicating the existence of residual structure in rVlambda6 proteins. However, the residual structure of Wil was markedly disrupted compared with those of the other proteins, despite there being no significant differences in amino acid sequences. Fibrillation experiments revealed that Wil had a longer lag time for fibril formation than the others. When the single disulfide bond was reduced and alkylated, the residual structure was largely disrupted and fibril formation was delayed in all three rVlambda6 proteins. It was suggested that the residual structure in highly unfolded state has a crucial role in amyloid fibril formation in many proteins, even pathogenic ones.
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PMID:Residual structures in the acid-unfolded states of Vlambda6 proteins affect amyloid fibrillation. 1964 48

Sugar-based osmolyte molecules are known to stabilize proteins under stress, but usually they have poor chaperone performance in inhibiting protein aggregation. Here, we show that the nanoparticle form of sugars molecule can enhance their chaperone performance typically by 102-105 times, compared to molecular sugar. Sugar-based plate-like nanoparticles of 20-40 nm hydrodynamic size have been synthesized by simple heating of acidic aqueous solution of glucose/sucrose/maltose/trehalose. These nanoparticles have excitation-dependent green/yellow/orange emission and surface chemistry identical to the respective sugar molecule. Fibrillation of lysozyme/insulin/amyloid beta in extracellular space, aggregation of mutant huntingtin protein inside model neuronal cell, and cytotoxic effect of fibrils are investigated in the presence of these sugar nanoparticles. We found that sugar nanoparticles are 102-105 times efficient than respective sugar molecules in inhibiting protein fibrillation and preventing cytotoxicity arising of fibrils. We propose that better performance of the nanoparticle form is linked to its stronger binding with fibril structure and enhanced cell uptake. This result suggests that nanoparticle form of osmolyte can be an attractive option in prevention and curing of protein aggregation-derived diseases.
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PMID:Sugar-Terminated Nanoparticle Chaperones Are 102-105 Times Better Than Molecular Sugars in Inhibiting Protein Aggregation and Reducing Amyloidogenic Cytotoxicity. 3143 2

Protein fibrillation is a challenging issue in medicine, causing many diseases, and an impediment to pharmaceutics and protein industry. Many chemicals, especially polyphenol compounds and aromatic small molecules, have been widely used as an effective strategy to combat protein fibril formation. Hence, understanding mechanisms of fibrillation inhibition and contributing forces in this process are significant. In this study, the inhibitory effect of paclitaxel on lysozyme fibrillation was investigated with respect to thermal and colloidal stability. Fibrillation was monitored with ThT fluorescence, circular dichroism, and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry and docking; thermal and colloidal stability with differential scanning calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme fibrillation, and interacted with lysozyme through hydrogen bonds and van der Waals' interactions. The viability of PC12 cells retrieved as a result of fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the aggregation-prone region of lysozyme and suppressed the effective interactions between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal stability, it increased lysozyme's colloidal stability by either increasing the surface charge density or charge distribution on lysozyme. In conclusion, our results suggest a model for paclitaxel's inhibitory role through two complementary steps driving to "off-pathway" oligomer formation and attenuation of fibril formation.
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PMID:Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers. 2935 77