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Article

Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease

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Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Anillo envolvente Pronaf y Estocolmo s/n, Ciudad Juarez, Chihuahua 32310, Mexico
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Department of Pharmacology, University of Nevada, Reno School of Medicine, Mailstop 318, Manville Building 19A(Office)/18(Lab), Reno, NV 89557, USA
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El Colegio de Chihuahua, Calle Partido Díaz 4723 esquina con Anillo Envolvente del Pronaf, colonia Progresista, Ciudad Juárez, Chihuahua 32310, Mexico
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Authors to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Int. J. Mol. Sci. 2016, 17(8), 1346; https://doi.org/10.3390/ijms17081346
Received: 29 June 2016 / Revised: 3 August 2016 / Accepted: 9 August 2016 / Published: 22 August 2016
(This article belongs to the Special Issue Neuronal Protein Homeostasis in Health and Disease)
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 (<10 µM) and plateaus at elevated concentrations (>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. View Full-Text
Keywords: 4-nitrophenyl acetate; human carboxyl esterase; redox sensor; oxidative stress; DJ1/PARK7; ROS; Parkinson’s disease 4-nitrophenyl acetate; human carboxyl esterase; redox sensor; oxidative stress; DJ1/PARK7; ROS; Parkinson’s disease
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MDPI and ACS Style

Vázquez-Mayorga, E.; Díaz-Sánchez, Á.G.; Dagda, R.K.; Domínguez-Solís, C.A.; Dagda, R.Y.; Coronado-Ramírez, C.K.; Martínez-Martínez, A. Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease. Int. J. Mol. Sci. 2016, 17, 1346. https://doi.org/10.3390/ijms17081346

AMA Style

Vázquez-Mayorga E, Díaz-Sánchez ÁG, Dagda RK, Domínguez-Solís CA, Dagda RY, Coronado-Ramírez CK, Martínez-Martínez A. Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease. International Journal of Molecular Sciences. 2016; 17(8):1346. https://doi.org/10.3390/ijms17081346

Chicago/Turabian Style

Vázquez-Mayorga, Emmanuel, Ángel G. Díaz-Sánchez, Ruben K. Dagda, Carlos A. Domínguez-Solís, Raul Y. Dagda, Cynthia K. Coronado-Ramírez, and Alejandro Martínez-Martínez. 2016. "Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease" International Journal of Molecular Sciences 17, no. 8: 1346. https://doi.org/10.3390/ijms17081346

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