التفاصيل البيبلوغرافية
| العنوان: |
Decoding allosteric regulation by the acyl carrier protein. |
| المؤلفون: |
Sztain, Terra, Bartholow, Thomas G., Lee, D. John, Casalino, Lorenzo, Mitchell, Andrew, Young, Megan A., Jianing Wang, McCammon, J. Andrew, Burkart, Michael D. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 4/20/2021, Vol. 118 Issue 16, p1-7, 7p |
| مصطلحات موضوعية: |
ACYL carrier protein, ALLOSTERIC regulation, MOLECULAR spectroscopy, CARRIER proteins, MOLECULAR dynamics, COMMERCIAL products |
| مستخلص: |
Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Płoskon et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)- dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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