Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a determinant of survival, immunity is likely to be significant in enabling coral larvae to disperse and successfully recruit, however, whether reef-building coral larvae have immune defenses is unknown. We investigated the potential presence and variation in immunity in the lecithotrophic larvae of Acropora tenuis through larval development. Enzymes indicative of tyrosinase and laccase-type melanin-synthesis were quantified, and the concentration of three coral fluorescent proteins was measured over six developmental stages; egg, embryo, motile planula, planula post-exposure to crustose coralline algae (CCA; settlement cue), settled, settled post-exposure to Symbiodinium (endosymbiont). Both types of melanin-synthesis pathways and the three fluorescent proteins were present in A. tenuis throughout development. Laccase-type activity and red fluorescence increased following exposure of planula to CCA, whereas tyrosinase-type activity and cyan fluorescence increased following settlement. No change was detected in the measured parameters following exposure to Symbiodinium. This study is the first to document coral larval immune responses and suggests the melanin-synthesis pathways have disparate roles-the laccase-type potentially non-immunological and the tyrosinase-type in cytotoxic defense. Our results indicate that corals have the potential to resist infection from the earliest life history phase.
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PMID:Immunity through early development of coral larvae. 2288 33

This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV-vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors.
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PMID:Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase. 2784 Feb 15

Misfolding and structural alteration in proteins lead to serious malfunctions and cause various diseases in humans. Mutations at the active binding site in tyrosinase impair structural stability and cause lethal albinism by abolishing copper binding. To evaluate the histidine mutational effect, all mutated structures were built using homology modelling. The protein sequence was retrieved from the UniProt database, and 3D models of original and mutated human tyrosinase sequences were predicted by changing the residual positions within the target sequence separately. Structural and mutational analyses were performed to interpret the significance of mutated residues (N180, R202, Q202, R211, Y363, R367, Y367 and D390) at the active binding site of tyrosinases. CSpritz analysis depicted that 23.25% residues actively participate in the instability of tyrosinase. The accuracy of predicted models was confirmed through online servers ProSA-web, ERRAT score and VERIFY 3D values. The theoretical pI and GRAVY generated results also showed the accuracy of the predicted models. The CCA negative correlation results depicted that the replacement of mutated residues at His within the active binding site disturbs the structural stability of tyrosinases. The predicted CCA scores of Tyr367 (-0.079) and Q/R202 (0.032) revealed that both mutations have more potential to disturb the structural stability. MD simulation analyses of all predicted models justified that Gln202, Arg202, Tyr367 and D390 replacement made the protein structures more susceptible to destabilization. Mutational results showed that the replacement of His with Q/R202 and Y/R363 has a lethal effect and may cause melanin associated diseases such as OCA1. Taken together, our computational analysis depicts that the mutated residues such as Q/R202 and Y/R363 actively participate in instability and misfolding of tyrosinases, which may govern OCA1 through disturbing the melanin biosynthetic pathway.
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PMID:Computational analysis of histidine mutations on the structural stability of human tyrosinases leading to albinism insurgence. 2864 Mar 9

Micro-molecular drugs have special advantages to cope with challenging diseases, however their structure, physical and chemical properties, stability, and pharmacodynamics have more requirements for the way they are delivered into the body. Carrier-based drug delivery systems can circumvent many limited factors of drug delivery and increase their bioavailability. In this context, stable drug nanocarriers of alkaline amino acids (arginine, Arg) modified conjugated linoleic acid-carboxymethyl chitosan (CLA-CMCS) conjugate were developed, which could generate supramolecular micelles to effectively encapsulate the tyrosinase inhibitor phenylethyl resorcinol (PR). The resulting CCA-NPs were spherical nanoparticles with a mean size around 175 nm. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cellular uptake investigation demonstrated that the CCA-NPs were non-cytotoxic and had excellent cell transport ability. In addition, these CCA-NPs were able to effectively deliver PR and inhibited melanin formation to reduce pigmentation by enhancing cellular uptake. In conclusion, our research indicated that nanocarriers based on self-assembly amphiphilic polymers constituted a promising and effective drug delivery system in hyperpigmentation targeting.
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PMID:Fabrication of Carboxylmethyl Chitosan Nanocarrier via Self-Assembly for Efficient Delivery of Phenylethyl Resorcinol in B16 Cells. 3205 46