Aldehyde-alcohol dehydrogenase undergoes structural transition to form extended spirosomes for substrate channeling
| العنوان: | Aldehyde-alcohol dehydrogenase undergoes structural transition to form extended spirosomes for substrate channeling |
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| المؤلفون: | Chaok Seok, Jin-Seok Choi, Gijeong Kim, Juwon Jang, Andrew J. Roe, Jinsol Yang, Ji-Joon Song, Olwyn Byron |
| المصدر: | Communications Biology, Vol 3, Iss 1, Pp 1-9 (2020) Communications Biology |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, Stereochemistry, Protein Conformation, Substrate channeling, Medicine (miscellaneous), Aldehyde dehydrogenase, Dehydrogenase, Reaction intermediate, Crystallography, X-Ray, General Biochemistry, Genetics and Molecular Biology, Article, Substrate Specificity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Escherichia coli, lcsh:QH301-705.5, 030304 developmental biology, Alcohol dehydrogenase, Organelles, 0303 health sciences, Cofactor binding, Aldehydes, biology, Ethanol, integumentary system, Chemistry, urogenital system, Escherichia coli Proteins, Cryoelectron Microscopy, digestive, oral, and skin physiology, Acetaldehyde, Alcohol Dehydrogenase, Substrate (chemistry), Aldehyde Oxidoreductases, lcsh:Biology (General), Enzyme mechanisms, biology.protein, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, hormones, hormone substitutes, and hormone antagonists |
| الوصف: | Aldehyde-alcohol dehydrogenase (AdhE) is an enzyme responsible for converting acetyl-CoA to ethanol via acetaldehyde using NADH. AdhE is composed of two catalytic domains of aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH), and forms a spirosome architecture critical for AdhE activity. Here, we present the atomic resolution (3.43 Å) cryo-EM structure of AdhE spirosomes in an extended conformation. The cryo-EM structure shows that AdhE spirosomes undergo a structural transition from compact to extended forms, which may result from cofactor binding. This transition leads to access to a substrate channel between ALDH and ADH active sites. Furthermore, prevention of this structural transition by crosslinking hampers the activity of AdhE, suggesting that the structural transition is important for AdhE activity. This work provides a mechanistic understanding of the regulation mechanisms of AdhE activity via structural transition, and a platform to modulate AdhE activity for developing antibiotics and for facilitating biofuel production. Using cryo-EM, Kim et al. show that aldehyde-alcohol dehydrogenase (AdhE) spirosomes undergo structural transition from compact to extended conformation from substrate binding. This transition opens up the substrate channel that transports the reaction intermediates to the next catalytic site. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2399-3642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6714591a5a5812f4d104e5ded0a55cba http://link.springer.com/article/10.1038/s42003-020-1030-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6714591a5a5812f4d104e5ded0a55cba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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