PTGES3L-AARSD1 Inhibitors

Chemical inhibitors of PTGES3L-AARSD1 can disrupt its function through a variety of mechanisms, primarily by interfering with the protein folding and degradation pathways within the cell. Trichostatin A, as a histone deacetylase inhibitor, can affect the acetylation state of histones, which in turn impacts the chaperone activity of PTGES3L-AARSD1. This is due to the fact that histone modification can influence the protein folding environment, potentially leading to an inhibition of the chaperone-like functions of PTGES3L-AARSD1. Similarly, geldanamycin and its analog 17-AAG, target the chaperone protein Hsp90, compromising its function. Since PTGES3L-AARSD1 is suggested to have a chaperone-like domain, the inhibition of Hsp90 can destabilize client proteins and disrupt the protein folding process that PTGES3L-AARSD1 may be involved in. Withaferin A and celastrol both inhibit the proteasome, which can lead to the accumulation of misfolded proteins, thus overwhelming the cellular protein folding machinery and indirectly inhibiting the function of PTGES3L-AARSD1.

Further compounding the stress on PTGES3L-AARSD1's chaperone-like activity, MG-132 and epoxomicin, both proteasome inhibitors, cause an accumulation of ubiquitinated proteins, which can disturb cellular proteostasis. This can overload PTGES3L-AARSD1's capacity to deal with misfolded proteins. Bortezomib, another proteasome inhibitor, impairs the degradation pathway of misfolded proteins, which can result in an increased load on PTGES3L-AARSD1. Concanamycin A disrupts protein trafficking by inhibiting V-ATPase, leading to an increase in misfolded proteins which may inhibit PTGES3L-AARSD1 indirectly. Lactacystin, like other proteasome inhibitors, also contributes to the functional inhibition of PTGES3L-AARSD1 by preventing the degradation of misfolded proteins. Lastly, puromycin disrupts protein synthesis, which can lead to an increased burden on the protein folding machinery of the cell, including PTGES3L-AARSD1, by causing an accumulation of proteins that have not been properly synthesized and folded.