Search results for "Tyrosinase"
showing 10 items of 64 documents
The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One
2017
Show your metal: l-Tyrosine is converted into the protective antioxidative polymer melanin in a sequence of reactions. In humans, the catalytic pathway starts with the tyrosinase HsTYR and two tyrosinase-related proteins HsTYRP1 and HsTYRP2. All three enzymes have the same active site but the latter two contain two zinc ions instead of copper ions.
Conversion of crustacean hemocyanin to catecholoxidase
2004
Crustacean hemocyanin as oxygen carrier and catecholoxidase as enzymes belong to the same protein family (type 3 copper proteins) sharing very similar active sites. Treatment with SDS of these hemocyanins results in an opening of the entrance to the active site for bulky phenolic compounds. This demonstrates, that almost all hemocyanin subunits possess the ability of catecholoxidase activity.
Dragon method for finding novel tyrosinase inhibitors: Biosilico identification and experimental in vitro assays
2006
QSAR (quantitative structure-activity relationship) studies of tyrosinase inhibitors employing Dragon descriptors and linear discriminant analysis (LDA) are presented here. A data set of 653 compounds, 245 with tyrosinase inhibitory activity and 408 having other clinical uses were used. The active data set was processed by k-means cluster analysis in order to design training and prediction series. Seven LDA-based QSAR models were obtained. The discriminant functions applied showed a globally good classification of 99.79% for the best model Class=-96.067+1.988 x 10(2)X0Av +9 1.907 BIC3 + 6.853 CIC1 in the training set. External validation processes to assess the robustness and predictive pow…
New tyrosinase inhibitors selected by atomic linear indices-based classification models.
2005
In the present report, the use of the atom-based linear indices for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones is presented. In this sense, discriminant models were applied and globally good classifications of 93.51% and 92.46% were observed for non-stochastic and stochastic linear indices best models, respectively, in the training set. The external prediction sets had accuracies of 91.67% and 89.44%. In addition, these fitted models were used in the screening of new cycloartane compounds isolated from herbal plants. A good behavior is shown between the theoretical and experimental results. These results provide a tool that can be used i…
Vanilloid Derivatives as Tyrosinase Inhibitors Driven by Virtual Screening-Based QSAR Models
2010
A number of vanilloids have been tested as tyrosinase inhibitors using Ligand-Based Virtual Screening (LBVS) driven by QSAR (Quantitative Structure-Activity Relationship) models as the multi-agent classification system. A total of 81 models were used to screen this family. Then, a preliminary cluster analysis of the selected chemicals was carried out based on their bioactivity to detect possible similar substructural features among these compounds and the active database used in the QSAR model construction. The compounds identified were tested in vitro to corroborate the results obtained in silico. Among them, two chemicals, isovanillin (K(M) (app) = 1.08 mM) near to kojic acid (reference d…
Atom-Based 2D Quadratic Indices in Drug Discovery of Novel Tyrosinase Inhibitors: Results ofIn Silico Studies Supported by Experimental Results
2007
Herein we present results of QSAR studies of tyrosinase inhibitors employing one of the atom-based TOMOCOMD-CARDD (acronym of TOpological MOlecular COMputer Design-Computer Aided “Rational” Drug Design) descriptors, molecular quadratic indices, and Linear Discriminant Analysis (LDA) as pattern recognition method. In this way, a database of 246 organic chemicals, reported as tyrosinase inhibitors having great structural variability, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. In total, 12 LDA-based QSAR models were obtained, the first six with the non-stochastic total and local quadratic indices and the six rema…
Indirect oxidation of amino acid phenylhydrazides by mushroom tyrosinase.
2006
We have investigated oxidation of amino acid phenylhydrazides by mushroom tyrosinase in the presence of 4-tert-butylcatechol and N-acetyl-l-tyrosine. Spectrophotometric measurements showed gradual disappearance of 4-tert-butyl-o-benzoquinone, generated by oxidation of 4-tert-butylcatechol with sodium periodate, after addition of amino acid phenylhydrazides. However, the presence of the phenylhydrazides did not influence the concentration of 4-tert-butyl-o-benzoquinone formed during enzymatic oxidation. Oxygen consumption measurements demonstrated that in a mixture both compounds were oxidized but the reaction rate was proportional to the concentration of the catechol. In the oxidation of N-…
Transporter (TAP)- and proteasome-independent presentation of a melanoma-associated tyrosinase epitope.
2000
The melanosomal protein tyrosinase is considered as a target of specific immunotherapy against melanoma. Two tyrosinase-derived peptides are presented in association with HLA-A2.1 [Wolfel et al., Eur. J. Immunol., 24, 759-764 (1994)]. Peptide 1-9 (MLLAVLYCL) is generated from the putative signal sequence. The internal peptide 369-377 is posttranslationally converted at residue 371, and its presentation is dependent on functional TAP transporters and proteasomes [Mosse et al., J. exp. Med.187, 37-48 (1998)]. Herein, we report on the processing and transport requirements for the signal sequence-derived peptide 1-9 that were studied in parallel to those for peptide 369-377. After infection of …
Kinetic properties of hexameric tyrosinase from the crustacean Palinurus elephas.
2008
Tyrosinases catalyze hydroxylation of monophenols to o-diphenols and their subsequent oxidation to o-quinones, whereas catecholoxidases catalyze only the latter reaction. Both enzymes occur in all organisms and are Type 3 copper proteins that perform the first steps of melanin formation. In arthropods, they play an essential role in the sclerotization of the exoskeleton. Very few phenoloxidases are characterized structurally or kinetically and the existence of an actual tyrosinase activity has not been demonstrated in most cases. Here we present for the first time a complete kinetic characterization of a tyrosinase from a crustacean (Palinurus elephas) including the influence of inhibitors.…