From Protease to Decarboxylase: THE MOLECULAR METAMORPHOSIS OF PHOSPHATIDYLSERINE DECARBOXYLASE.

The Journal of Biological Chemistry
Jae-Yeon ChoiDennis R Voelker

Abstract

Phosphatidylserine decarboxylase (PSDs) play a central role in the synthesis of phosphatidylethanolamine in numerous species of prokaryotes and eukaryotes. PSDs are unusual decarboxylase containing a pyruvoyl prosthetic group within the active site. The covalently attached pyruvoyl moiety is formed in a concerted reaction when the PSD proenzyme undergoes an endoproteolytic cleavage into a large β-subunit, and a smaller α-subunit, which harbors the prosthetic group at its N terminus. The mechanism of PSD proenzyme cleavage has long been unclear. Using a coupled in vitro transcription/translation system with the soluble Plasmodium knowlesi enzyme (PkPSD), we demonstrate that the post-translational processing is inhibited by the serine protease inhibitor, phenylmethylsulfonyl fluoride. Comparison of PSD sequences across multiple phyla reveals a uniquely conserved aspartic acid within an FFXRX6RX12PXD motif, two uniquely conserved histidine residues within a PXXYHXXHXP motif, and a uniquely conserved serine residue within a GS(S/T) motif, suggesting that PSDs belong to the D-H-S serine protease family. The function of the conserved D-H-S residues was probed using site-directed mutagenesis of PkPSD. The results from these mutagenesi...Continue Reading

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Citations

Jun 14, 2017·Molecular and Cellular Biology·Oluwaseun B OgunbonaSteven M Claypool
Oct 6, 2018·The Journal of Biological Chemistry·Nicole KilianChoukri Ben Mamoun
Apr 2, 2015·The Journal of Biological Chemistry·Ouma OngukaSteven M Claypool
Feb 23, 2020·Annual Review of Biochemistry·Soni DeshwalThomas Langer
Dec 17, 2017·The Journal of Biological Chemistry·Jae-Yeon ChoiDennis R Voelker
Oct 5, 2018·Evolution Letters·Hannah T ReynoldsJason C Slot
May 25, 2021·Frontiers in Molecular Biosciences·Yasmine HassounEmmanuelle Bouveret
Sep 11, 2019·ACS Chemical Biology·Pingdewinde N SamSteven M Claypool

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