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-Structure paper
タイトル | Atomic Resolution Cryo-EM Structure of β-Galactosidase. |
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ジャーナル・号・ページ | Structure, Vol. 26, Issue 6, Page 848-856.e3, Year 2018 |
掲載日 | 2018年6月5日 |
著者 | Alberto Bartesaghi / Cecilia Aguerrebere / Veronica Falconieri / Soojay Banerjee / Lesley A Earl / Xing Zhu / Nikolaus Grigorieff / Jacqueline L S Milne / Guillermo Sapiro / Xiongwu Wu / Sriram Subramaniam / |
PubMed 要旨 | 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- ...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. |
リンク | Structure / PubMed:29754826 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 1.9 Å |
構造データ | |
化合物 | ChemComp-PTQ: ChemComp-MG: ChemComp-NA: ChemComp-HOH: |
由来 |
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キーワード | HYDROLASE / drift correction / radiation damage / drug discovery / precision medicine / computer-aided drug discovery |