Transient conformations in the unliganded FK506 binding domain of FKBP51 correspond to two distinct inhibitor-bound states.

ABSTRACT: Members of the FK506-binding protein (FKBP) family regulate a range of important physiological processes. Unfortunately, current therapeutics such as FK506 and rapamycin exhibit only modest selectivity among these functionally distinct proteins. Recent progress in developing selective inhibitors has been reported for FKBP51 and FKBP52, which act as mutual antagonists in the regulation of steroid hormone signaling. Two structurally similar inhibitors yield distinct protein conformations at the binding site. Localized conformational transition in the binding site of the unliganded FK1 domain of FKBP51 is suppressed by a K58T mutation that also suppresses the binding of these inhibitors. Here, it is shown that the changes in amide hydrogen exchange kinetics arising from this K58T substitution

SUBMITTER: Anderson JS 

PROVIDER: S-EPMC10514456 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature