التفاصيل البيبلوغرافية
| العنوان: |
Control of Unsaturation in De Novo Fatty Acid Biosynthesis by FabA |
| المؤلفون: |
Bartholow, Thomas G, Sztain, Terra, Young, Megan A, Lee, D John, Davis, Tony D, Abagyan, Ruben, Burkart, Michael D |
| المصدر: |
Biochemistry, vol 61, iss 7 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2022 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Acyl Carrier Protein, Escherichia coli, Fatty Acid Synthase, Type II, Fatty Acids, Unsaturated, Hydro-Lyases, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology |
| جغرافية الموضوع: |
608 - 615 |
| الوصف: |
Carrier protein-dependent biosynthesis provides a thiotemplated format for the production of natural products. Within these pathways, many reactions display exquisite substrate selectivity, a regulatory framework proposed to be controlled by protein-protein interactions (PPIs). In Escherichia coli, unsaturated fatty acids are generated within the de novo fatty acid synthase by a chain length-specific interaction between the acyl carrier protein AcpP and the isomerizing dehydratase FabA. To evaluate PPI-based control of reactivity, interactions of FabA with AcpP bearing multiple sequestered substrates were analyzed through NMR titration and guided high-resolution docking. Through a combination of quantitative binding constants, residue-specific perturbation analysis, and high-resolution docking, a model for substrate control via PPIs has been developed. The in silico results illuminate the mechanism of FabA substrate selectivity and provide a structural rationale with atomic detail. Helix III positioning in AcpP communicates sequestered chain length identity recognized by FabA, demonstrating a powerful strategy to regulate activity by allosteric control. These studies broadly illuminate carrier protein-dependent pathways and offer an important consideration for future inhibitor design and pathway engineering. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt4ww3w23p; https://escholarship.org/uc/item/4ww3w23pTest |
| الإتاحة: |
https://escholarship.org/uc/item/4ww3w23pTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.8F719739 |
| قاعدة البيانات: |
BASE |
