Disease relevance of PSD1

• The deduced amino acid sequence shows significant identity (34%) to a PSD-like sequence from Clostridium pasteurianum and the yeast PSD1 (19%) at the carboxyl end of the protein [1].
• A gene (PSD1) encoding a phosphatidylserine decarboxylase of Saccharomyces cerevisiae was cloned by complementation of a conditional lethal mutation in the homologous gene in Escherichia coli strain EH150 [2].

High impact information on PSD1

• Genetic manipulations to increase phosphatidylethanolamine levels in gpi7Delta cells by overexpression of PSD1 restore cell growth at 37 degrees C without restoring the addition of a substituent to Man2 [3].
• Similar to phb mutants, deletion of PSD1 destabilizes polypeptides encoded by the mitochondrial genome [4].
• The majority of mitochondrial phosphatidylethanolamine (PtdEtn), a phospholipid essential for aerobic growth of yeast cells, is synthesized by phosphatidylserine decarboxylase 1 (Psd1p) in the inner mitochondrial membrane (IMM) [4].
• Phosphatidylserine (PtdSer) synthesized in the endoplasmic reticulum and related membranes (mitochondria-associated membrane (MAM)) is transported to the mitochondria by unknown gene products and decarboxylated to form phosphatidylethanolamine at the inner membrane by PtdSer decarboxylase 1 (Psd1p) [5].
• When the PSD1 gene is deleted, the resultant strain (psd1Delta) grows normally at 30 degrees C in glucose and in the absence of exogenous choline or ethanolamine [6].

Biological context of PSD1

• Suppressors commonly effective to mpc1-4 and mpc1-5 mutations are PSD1, encoding phosphatidylserine decarboxylase, and ECM33, which were found to suppress the temperature-sensitive phenotype shown by the fsr2-1 and las21delta mutants, those of which have defects in the GPI anchor synthesis [7].
• Disruption of the PSD1 gene in a haploid strain of yeast resulted in loss of detectable decarboxylase activity but little alteration of the growth properties or phospholipid composition [2].
• Two yeast enzymes, Psd1p and Psd2p, catalyze the decarboxylation of phosphatidylserine to produce phosphatidylethanolamine (PtdEtn) [6].

Anatomical context of PSD1

• These observations suggest that Mpc1 preferentially utilizes phosphatidylethanolamine produced by Psd2 that is localized in Golgi/vacuole. fsr2-1 dpl1 Delta psd1delta strains showed slower growth than fsr2-1 dpl1delta psd2 delta, suggesting that Fsr2 enzyme depends more on Dpl1 and Psd1 for production of phosphatidylethanolamine [7].
• We have designed a screen for strains defective in PtdSer transport (pstA mutants) between the endoplasmic reticulum and Psd1p that relies on isolating ethanolamine auxotrophs in suitable (psd2Delta) genetic backgrounds [5].

Associations of PSD1 with chemical compounds

• I report that the major mitochondrial PS decarboxylase gene (PSD1) is transcriptionally regulated by inositol in a manner similar to that reported for other coregulated phospholipid biosynthetic genes [8].
• PtdEtn produced by Psd1p and Psd2p can be transported to the ER, where it is methylated to form PtdCho [9].
• On further purification by reverse-phase high performance liquid chromatography, two small cysteine-rich polypeptides were obtained (Psd1 and Psd2) [10].

Other interactions of PSD1

• These data indicate that the gene isolated is the structural gene for PSD2 and that the PSD1 and PSD2 enzymes account for all yeast PSD activity [1].
• I show that the presence of a functional major mitochondrial PS decarboxylase encoded by the PSD1 gene is necessary for proper regulation of INO1 in response to inositol in the absence of ethanolamine [8].

Analytical, diagnostic and therapeutic context of PSD1

• Circular dichroism, intrinsic fluorescence, and nuclear magnetic resonance spectroscopy analysis indicated that the recombinant protein has a very similar folding and a correct disulfide-bonding pattern when compared to native Psd1 [11].

References