One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein Sites
Year: 2015
Type: article
Abstract: Interrogating fragment libraries by X-ray crystallography is a powerful strategy for discovering allosteric ligands for protein targets. Cryocooling of crystals should theoretically increase the fraction of occupied binding sites and decrease radiation damage. However, it might also perturb protein conformations that can be accessed at room temperature. Using data from crystals measured consecutively at room temperature and at cryogenic temperature, we found that transient binding sites could be abolished at the cryogenic temperatures employed by standard approaches. Changing the temperature at which the crystallographic data was collected could provide a deliberate perturbation to the equilibrium of protein conformations and help to visualize hidden sites with great potential to allosterically modulate protein function.
Source: ChemBioChem
Institution: University of California, San Francisco
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Awards: G1286236842, G1286251239, G1863003419, G2756012592, G30714459, G3083819904, G3525532610, G382641700, G42916606, G5652362427, G650090426, G6730734543, Design and Experimental Testing of New Docking Methods, The Impact of Mutation on the Conformations and Recognition of Ubiquitin, Model Comparison in Structural Biology, Biology with X-ray Lasers, G969889393
OpenAlex ID: W1850462267