Protein tyrosine phosphatases (PTPs) of the polymerase and histidinol phosphatases (PHP) superfamily with characteristic phosphatase activity dependent on divalent metal ions are found in many gram-positive bacteria. Although members of this family are co-purified with metal ions, they still require the exogenous supply of metal ions for full activation. However, the specific roles these metal ions play during catalysis are yet to be well understood. Here, we report the metal ion requirement for phosphatase activities of S. aureus Cap8C and L. rhamnosus Wzb. AlphaFold-predicted structures of the two PTPs suggest that they are members of the PHP family. Like other PHP phosphatases, the two enzymes have catalytic preference for Mn2+, Co2+, and Ni2+ ions. Cap8C and Wzb show an unusual thermophilic property with optimum activities over 75oC. Pre-incubation experiments show that the two enzymes are not inherently thermostable suggesting that certain catalytic step(s) in the reaction mechanism has a high activation energy. Consistent with this model, the activity-temperature profiles of the two enzymes are dependent on the divalent metal ion activating the enzyme.

Our target point within this following steps, is prostate cancer. Phosphatases are implicated in differents cell alterations, including proliferation, differentiation and carcinogenesis. In specific life circumstances, proteins are regulators with implications in intracellular signaling pathways. Alterations in phosphatases functionality represent a key point in malignancy development. We try within our description, to focus on an important process refering to dysregulation of phosphatase activity. More than, we will discuss therapeutic key points refering to compounds that inhibits phosphatase proteins with implications in carcinogenesis. So finally after folowing describtion steps, purposed aim is to conclude on prostate cancer and different key points abordation.

As part of the ongoing screening research for local edible plants in Thailand, Petroselinum crispum fruit oil was considered as a potential bioinsecticide with proven antimosquito activity against both the pyrethroid susceptible and resistant strains of Aedes aegypti. Due to the comparative mosquitocidal efficacy on these mosquitoes, this plant oil is promoted as a natural alternative and attractive candidate for further study in monitoring resistance of mosquito vectors. Therefore, the aim of this study was to evaluate the impact of P. crispum oil on the biochemical characteristics of the target mosquito larvae of Ae. aegypti, by determining quantitative changes of key enzymes responsible for xenobiotic detoxification, including glutathione-S-transferases (GSTs), α- and β-esterases (α-/β-ESTs), acetylcholinesterase (AChE), acid and alkaline phosphatases (ACP and ALP) and mixed-function oxidases (MFO). Three populations of Ae. aegypti, comprising the pyrethroid susceptible Muang Chiang Mai-susceptible (MCM-S) strain and the pyrethroid resistant Pang Mai Dang-resistant (PMD-R) and Upakut-resistant (UPK-R) strains, were used as test organisms. Biochemical study of Ae. aegypti larvae prior to treatment with P. crispum oil revealed that apart from AChE, the baseline activity of most defensive enzymes, such as GSTs, α-/β-ESTs, ACP, ALP and MFO, in resistant UPK-R or PMD-R, was higher than that determined in susceptible MCM-S. However, after 24-h exposure to P. crispum oil, the pyrethroid susceptible and resistant Ae. aegypti showed similarity in biochemical features, with alterations of enzyme activity in the treated larvae, as compared to the controls. A significant increase in the activity levels of GSTs, α-/β-ESTs, ACP and ALP was recorded in all strains of P. crispum oil-treated Ae. aegypti larvae, whereas MFO and AChE activity in these mosquitoes was decreased. The recognizable larvicidal capability on pyrethroid resistant Ae. aegypti, and the inhibitory effect on AChE and MFO, emphasized the potential of P. crispum oil as an attractive alternative application for management of mosquito resistance in current and future control programs.

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

The receptor-type protein tyrosine phosphatases (RPTPs) are involved in a wide variety of physiological functions which are mediated via their diverse extracellular regions. They play key roles in cell-cell contacts, bind various ligands and are regulated by dimerization and other processes. Depending on the subgroup they have been described as everything from ‘rigid rods’ to ‘floppy tentacles’. Here we review current experimental structural knowledge on the extracellular region of RPTPs and draw on AlphaFold structural predictions to provide further insights into structure and function of these cellular signalling molecules.