Sandbox Reserved 1767: Difference between revisions

The Protein phosphatase complex 1 (PP1C) subunit contains the catalytic site of the SMP complex. The PP1C subunit is a phosphatase enzyme responsible for the removal of a phosphate group on the N-terminal phosphoserine (NTpS) of RAF (Ser259).<ref name="Liau">PMID: 35768504</ref>. The exact mechanism of dephosphorylation is currently unknown, but there are three catalytic metal ions: 2 Mn2+ and 1 Cl- present that coordinate nucleophilic water molecules in the active site. This dephosphorylation event allows for pathway activation. Although PP1C can dephosphorylate other proteins independently from the SMP complex, it cannot act on Raf unless bound to the complex because it lacks intrinsic substrate selectivity.<ref name="Liau">PMID: 35768504</ref> SHOC2 and MRAS aid in the specificity of the enzymatic activity. Hence, PP1C requires the presence of SHOC2 and MRAS to be function. <ref name="Hauseman">PMID:35830882</ref> PP1C binds to SHOC2 and MRAS-GTP in a specific orientation that doesn’t change the conformation of the catalytic site and leaves it accessible for substrate binding.

PP1C binds to SHOC2 through a hydrophobic n-terminal disordered region that is complimentary to the RVXF motif on SHOC2. GREEN LINK or picture? Similarly to SHOC2, PP1C does not undergo a significant conformational change when SHOC2 and MRAS-GTP bind. The lack of conformational change shows that the structure of PP1C is not dependent on the SMP complex, but in order to act as a phosphatase it must be bound to the complex.<ref name="Liau">PMID: 35768504</ref>.  

The substrate binds through hydrogen bonds with the main chain and side chain atoms of the catalytic residues **insert residue numbers here**. Mutations in the active site lead to increased activity, causing the Ras/Raf signaling cascade to be triggered more frequently.<ref name="Hurley">PMID: 17636256</ref> ***insert what residues are mutated and HOW it leads to more activity.