Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B.

ABSTRACT: Much of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously, we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy et al., 2018). Here, we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of a diverse library of ligands to date

SUBMITTER: Skaist Mehlman T 

PROVIDER: S-EPMC9991056 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature