Atomic Resolution Cryo-EM Structure of ß-Galactosidase.
Structure
; 26(6): 848-856.e3, 2018 06 05.
Article
en En
| MEDLINE
| ID: mdl-29754826
ABSTRACT
The advent of direct electron detectors has enabled the routine use of single-particle cryo-electron microscopy (EM) approaches to determine structures of a variety of protein complexes at near-atomic resolution. Here, we report the development of methods to account for local variations in defocus and beam-induced drift, and the implementation of a data-driven dose compensation scheme that significantly improves the extraction of high-resolution information recorded during exposure of the specimen to the electron beam. These advances enable determination of a cryo-EM density map for ß-galactosidase bound to the inhibitor phenylethyl ß-D-thiogalactopyranoside where the ordered regions are resolved at a level of detail seen in X-ray maps at â¼ 1.5 Å resolution. Using this density map in conjunction with constrained molecular dynamics simulations provides a measure of the local flexibility of the non-covalently bound inhibitor and offers further opportunities for structure-guided inhibitor design.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiogalactósidos
/
Beta-Galactosidasa
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos