An essential role of acetyl coenzyme A in the catalytic cycle of insect arylalkylamine N-acetyltransferase
| Autor: | Wei-Cheng Ding, Hui-Chun Cheng, Yi-Chen Yang, I-Chen Hu, Chih-Hsuan Lai, Chu-Ya Wu, Yi-Chung Liu, Ping-Chiang Lyu, Yi-Zong Lee |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Insecta QH301-705.5 Stereochemistry AANAT Protein Conformation Medicine (miscellaneous) Arylalkylamine N-Acetyltransferase General Biochemistry Genetics and Molecular Biology Cofactor Article Catalysis Substrate Specificity 03 medical and health sciences Structure-Activity Relationship Acetyl Coenzyme A Catalytic Domain Animals Biogenic Monoamines Biology (General) 030304 developmental biology 0303 health sciences biology Chemistry fungi 030302 biochemistry & molecular biology Substrate (chemistry) Isothermal titration calorimetry Acetylation Nuclear magnetic resonance spectroscopy Catalytic cycle biology.protein Arylalkylamine Biocatalysis General Agricultural and Biological Sciences |
| Zdroj: | Commun Biol Communications Biology, Vol 3, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2399-3642 |
| Popis: | Acetyl coenzyme A (Ac-CoA)-dependent N-acetylation is performed by arylalkylamine N-acetyltransferase (AANAT) and is important in many biofunctions. AANAT catalyzes N-acetylation through an ordered sequential mechanism in which cofactor (Ac-CoA) binds first, with substrate binding afterward. No ternary structure containing AANAT, cofactor, and substrate was determined, meaning the details of substrate binding and product release remain unclear. Here, two ternary complexes of dopamine N-acetyltransferase (Dat) before and after N-acetylation were solved at 1.28 A and 1.36 A resolution, respectively. Combined with the structures of Dat in apo form and Ac-CoA bound form, we addressed each stage in the catalytic cycle. Isothermal titration calorimetry (ITC), crystallography, and nuclear magnetic resonance spectroscopy (NMR) were utilized to analyze the product release. Our data revealed that Ac-CoA regulates the conformational properties of Dat to form the catalytic site and substrate binding pocket, while the release of products is facilitated by the binding of new Ac-CoA. Wu et al. provide insight to the role of acetyl coenzyme A in regulating N-acetylation in insect AANAT using ITC and NMR methods. These results provide useful data on the structural function of insect AANATs. |
| Databáze: | OpenAIRE |
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