Cooperative dynamics across distinct structural elements regulate PTP1B activity

C ILV constant-time Carr-Purcell-Meiboom-Gill relaxation measurements experiments, we demonstrated that all four catalytically important loops-the WPD, Q, E, and substrate-binding loops-work in dynamic unity throughout the catalytic cycle of PTP1B. Thus, these data show that PTP1B activity is not controlled by a single functional element, but instead all key elements are dynamically coordinated. Together, these data provide the first fully comprehensive picture on how the validated drug target PTP1B functions.