Finding the mechanism of esterase D activation by a small molecule |
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| Affiliation: | 1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China;2. Hubei Key Laboratory of Edible Wild Plants Conservation & Utilization, National Demonstration Center for Experimental Biology Education, School of Life Science, Hubei Normal University, Huangshi 435002, PR China;3. Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, PR China;4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan 250012, PR China;1. Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;2. Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 30-343 Kraków, Poland;1. School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand;2. The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand;3. Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand;4. School of Biological Sciences, The University of Auckland, 3A Symonds St, Auckland 1010, New Zealand;1. ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia;2. School of Biological Sciences, Department of Molecular and Cellular Biology, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia |
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| Abstract: | People with reduced esterase D (ESD) activity are susceptible to many diseases. However, how to activate ESD is still unknown. To address the question, we identified that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) could be a good candidate activator for ESD activity. We found that FPD5 could increase ESD activity in a dose-dependent way. FPD5 bound directly to ESD at Lys180 rather than its ubiquitination site Lys213. Site-directed mutagenesis at the binding site or the ubiquitination site inhibited FPD5 action. FPD5 increased the level of ESD mono-ubiquitination and mutESD K213A completely inhibited this action. Our findings highlighted the activation mechanism of ESD via promoting the mono-ubiquitination of ESD. |
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| Keywords: | ESD activation FPD5 Mono-ubiquitination |
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