Last update 01 Nov 2024

ABHD10

Last update 01 Nov 2024

Basic Info

Synonyms

ABHD10, abhydrolase domain containing 10, depalmitoylase, Abhydrolase domain-containing protein 10

+ [5]

Introduction

Acts as an acyl-protein thioesterase that hydrolyzes fatty acids from acylated residues in proteins (PubMed:31740833). Regulates the mitochondrial S-depalmitoylation of the nucleophilic active site residue of peroxiredoxin-5/PRDX5, a key antioxidant protein, therefore modulating mitochondrial antioxidant ability (PubMed:31740833). Also catalyzes the deglucuronidation of mycophenolic acid acyl-glucuronide, an active metabolite of the immunosuppressant drug mycophenolate (PubMed:22294686).

Drugs associated with ABHD10

ML257

Target

ABHD10

Mechanism

ABHD10 inhibitors

Active Org.

The Scripps Research Institute

Originator Org.

The Scripps Research Institute

Active Indication

Malignant glioma of brain

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ABHD10

100 Translational Medicine associated with ABHD10

0 Patents (Medical) associated with ABHD10

Literatures (Medical) associated with ABHD10

01 Apr 2024·International Journal of Biological Macromolecules

Targeted inhibition of gut bacterial β-glucuronidases by octyl gallate alleviates mycophenolate mofetil-induced gastrointestinal toxicity

Article

Author: Gao, Ang ; Yu, Yong-Xin ; Zhou, Shi-Ying ; Ren, Hao ; He, Qian ; Lian, Xin-Lei ; Xia, Li-Juan ; Wan, Lei ; Sun, Jian ; Qiu, Wei ; Zhao, Dong-Hao ; Liu, Ya-Hong ; Li, Gong ; Liao, Xiao-Ping

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated β-glucuronidase (βGUS). Therefore, controlling microbiota-produced βGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.

03 Jul 2023·Communications biology

The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease.

Article

Author: Zhang, Cong-Ying ; Zhou, Jing ; Wang, Wen-Tao ; Shi, Tie-Wei ; Bai, Chun-Ying ; Li, Tian-Zhu ; Wu, Bao

Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor β1 (TGFβ1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of α/β hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFβ1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5's Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.

01 Dec 2019·Nature Chemical BiologyQ1 · BIOLOGY

ABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5

Q1 · BIOLOGY

Article

Author: Qiu, Tian ; Kathayat, Rahul S ; Dickinson, Bryan C ; Fukata, Masaki ; Thorne, Anneke K ; Cao, Yang ; Fukata, Yuko ; Azizi, Saara-Anne ; Ahn, Daniel ; Rice, Phoebe A

S-Palmitoylation is a reversible lipid post-translational modification that has been observed on mitochondrial proteins, but both the regulation and functional consequences of mitochondrial S-palmitoylation are poorly understood. Here, we show that perturbing the 'erasers' of S-palmitoylation, acyl protein thioesterases (APTs), with either pan-active inhibitors or a mitochondrial-targeted APT inhibitor, diminishes the antioxidant buffering capacity of mitochondria. Surprisingly, this effect was not mediated by the only known mitochondrial APT, but rather by a resident mitochondrial protein with no known endogenous function, ABHD10. We show that ABHD10 is a member of the APT family of regulatory proteins and identify peroxiredoxin-5 (PRDX5), a key antioxidant protein, as a target of ABHD10 S-depalmitoylase activity. We then find that ABHD10 regulates the S-palmitoylation status of the nucleophilic active site residue of PRDX5, providing a direct mechanistic connection between ABHD10-mediated S-depalmitoylation of PRDX5 and its antioxidant capacity.

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ABHD10

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