# Dissecting the functional behavior of the differentially phosphorylated prolyl isomerase, Pin1

## TL;DR

This paper investigates how phosphorylation affects the function of the enzyme Pin1, revealing a sequence of events that leads to its deactivation.

## Contribution

The study identifies a phosphorylation sequence on Pin1 that deactivates its isomerase activity before affecting substrate binding.

## Key findings

- Ser71 phosphorylation precedes Ser16 phosphorylation in Pin1.
- Phosphorylation sequence leads to deactivation of Pin1's isomerase activity.
- Findings highlight the regulatory mechanisms of Pin1 in health and disease.

## Abstract

Protein post‐translational modifications (PTMs) play an intricate role in a diverse range of cellular processes creating a complex PTM code that governs cell homeostasis. Understanding the molecular build‐up and the critical factors regulating this PTM code is essential for targeted therapeutic design whereby PTM mis‐regulation is prevalent. Here, we focus on Pin1, a peptidyl‐prolyl cis‐trans isomerase whose regulatory function is altered by a diverse range of PTMs. Through employing advanced mass spectrometry techniques in combination with fluorescence polarization and enzyme activity assays, we elucidate the impact of combinatorial phosphorylation on Pin1 function. Moreover, two phosphorylation sites were identified whereby Ser71 phosphorylation preceded Ser16 phosphorylation, leading to the deactivation of Pin1's prolyl isomerase activity before affecting substrate binding. Together, these findings shed light on the regulatory mechanisms underlying Pin1 function and emphasize the importance of understanding PTM landscapes in health and disease.