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Atomic Resolution Cryo-EM Structure of β-Galactosidase.
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 β-galactosidase bound to the inhibitor phenylethyl β-D-thiogalactopyranoside where the ordered regions are resolved at a level of detail seen in X-ray maps at ∼ 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.
Duke Scholars
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Related Subject Headings
- beta-Galactosidase
- Thiogalactosides
- Protein Conformation
- Molecular Dynamics Simulation
- Models, Molecular
- Drug Design
- Crystallography, X-Ray
- Cryoelectron Microscopy
- Biophysics
- Binding Sites
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1878-4186&client=dukeuniv)
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- beta-Galactosidase
- Thiogalactosides
- Protein Conformation
- Molecular Dynamics Simulation
- Models, Molecular
- Drug Design
- Crystallography, X-Ray
- Cryoelectron Microscopy
- Biophysics
- Binding Sites