E-resources
-
One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein SitesFischer, Marcus; Shoichet, Brian K.; Fraser, James S.
Chembiochem : a European journal of chemical biology, July 27, 2015, Volume: 16, Issue: 11Journal Article
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. Too cool to show up: The common practice of cryocooling crystals was found to mask transient protein conformations. Data collected on a single crystal revealed ligand binding to a cryptic site at room temperature that was hidden at cryogenic temperature. These results contradict thermodynamic expectations and provide a method for discovering allosteric sites with great potential for modulating protein (mal)‐function.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.