Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease
| العنوان: | Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease |
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| المؤلفون: | Alejandro Martínez-Martínez, Raul Y. Dagda, Cynthia K. Coronado-Ramírez, Carlos A. Domínguez-Solís, Ruben K. Dagda, Emmanuel Vázquez-Mayorga, Ángel G. Díaz-Sánchez |
| المصدر: | International Journal of Molecular Sciences, Vol 17, Iss 8, p 1346 (2016) International Journal of Molecular Sciences; Volume 17; Issue 8; Pages: 1346 International Journal of Molecular Sciences |
| بيانات النشر: | MDPI AG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_treatment, Protein Deglycase DJ-1, Mutant, medicine.disease_cause, Esterase, Nitrophenols, 4-nitrophenyl acetate, human carboxyl esterase, redox sensor, oxidative stress, DJ1/PARK7, ROS, Parkinson’s disease, lcsh:Chemistry, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, Chemistry, Esterases, Parkinson Disease, General Medicine, Computer Science Applications, Molecular Docking Simulation, Biochemistry, Oxidation-Reduction, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, Reactive oxygen species, Protease, Organic Chemistry, PARK7, Cooperative binding, Hydrogen Peroxide, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Mutation, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress |
| الوصف: | Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson’s disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein). hDJ-1 showed maximum reaction velocity esterase activity (Vmax = 235.10 ± 12.00 U/mg protein), with a sigmoidal fit (S0.5 = 0.55 ± 0.040 mM) and apparent positive cooperativity (Hill coefficient of 2.05 ± 0.28). A PD-associated mutant of DJ-1 (M26I) lacked activity. Unlike its protease activity which is inactivated by reactive oxygen species (ROS), esterase activity of hDJ-1 is enhanced upon exposure to low concentrations of hydrogen peroxide (100 µM) suggesting that its activity is resistant to oxidative stress. Esterase activity of DJ-1 requires oxidation of catalytic cysteines, as chemically protecting cysteines blocked its activity whereas an oxido-mimetic mutant of DJ-1 (C106D) exhibited robust esterase activity. Molecular docking studies suggest that C106 and L126 within its catalytic site interact with esterase substrates. Overall, our data show that hDJ-1 contains intrinsic redox-sensitive esterase activity that is abolished in a PD-associated mutant form of the hDJ-1 protein. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af03698a60cd204cc6e966014f925f31Test http://www.mdpi.com/1422-0067/17/8/1346Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....af03698a60cd204cc6e966014f925f31 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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