[1] PPIase enzymes catalyze the transition of proline between cis and trans isomers and are essential to the numerous biological functions controlled and affected by prolyl isomerization (i.e. cell signalling, protein folding, and epigenetic modifications)[2] Without PPIases, prolyl peptide bonds will slowly switch between cis and trans isomers, a process that can lock proteins in a nonnative structure that can affect render the protein temporarily ineffective.
Although this switch can occur on its own, PPIases are responsible for most isomerization of prolyl peptide bonds.
[3] Most of these biological functions are affected by the isomerization of proline when one isomer interacts differently than the other, commonly causing an activation/deactivation relationship.
This aids in the multitude of effects that isomerization of proline can have in different biological mechanisms and functions.
One of the most studied cell signaling phenomena involving proline is the interactions with p53 and prolyl isomerases, specifically Pin1.
proline residues are found throughout the p53 proteins and without the phosphorylation and isomerization of specific Serine/Threonine-Proline motifs within p53, they cannot exhibit control over their target genes.
Fpr4 is a PPIase, in the FK507BP group, that exhibits catalytic activity at the proline positions 16, 30, and 38 (also written P16, P30, and P38 respectively) on the N-terminal region of histone H3 in Saccharomyces cerevisiae.
[6] Histone H3 has an important lysine residue at the 36 position (also written K36) on the N-terminal tail which can be methylated by Set2, a methyltransferase.
This can cause a decrease the ability of proteins to bind to the DNA and to the histone tail, including preventing Set2 from methylating K36.
[9] In mammalian cells, the isomerization of H3P30 interacts with the phosphorylation of H3S28 (serine in the 28 position of histone H3) and the methylation of H3K27.
The isomerization of the peptide bond between histone H3's alanine 15 and proline 16 is affected by the acetylation at K14 and can control the methylation states of K4.
[3][11] K4me3 represses gene transcription and depends upon the Set1 methyltransferase complex subunit Spp1 being balanced with the Jhd2 demethylases for proper function.
[12] PPIases target RNA polymerase II by interacting with the Rpb1 carboxy terminal domain, or CTD.
Nrd1 is a protein that is responsible for many of the transcriptional activities of RNAP II, specifically through the Nrd1- dependent termination pathway.
[9][13] Phosphorylated amino acids are crucial for the modulation of the binding of transcription factors and other gene regulatory proteins.