6NY9

Alpha/beta hydrolase domain-containing protein 10 from mouse

Summary for 6NY9

• Entry DOI: 10.2210/pdb6ny9/pdb
• Descriptor: Mycophenolic acid acyl-glucuronide esterase, mitochondrial, (4S)-2-METHYL-2,4-PENTANEDIOL, STRONTIUM ION, ... (4 entities in total)
• Functional Keywords: alpha/beta hydrolase, depalmitoylase, mitochondria, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 28289.97

Authors

Cao, Y.,Rice, P.A.,Dickinson, B.C. (deposition date: 2019-02-11, release date: 2020-01-22, Last modification date: 2023-10-11)

Primary citation

Cao, Y.,Qiu, T.,Kathayat, R.S.,Azizi, S.A.,Thorne, A.K.,Ahn, D.,Fukata, Y.,Fukata, M.,Rice, P.A.,Dickinson, B.C.
ABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5.
Nat.Chem.Biol., 15:1232-1240, 2019

PubMed Abstract: 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.

PubMed: 31740833
DOI: 10.1038/s41589-019-0399-y

Experimental method

X-RAY DIFFRACTION (1.66 Å)