Recognition mechanism of carrier protein by acyltransferase
| Project/Area Number |
17K07747
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 結晶構造解析 / ポリケタイド / 微生物酵素 / タンパク質間相互作用 / クロスリンク / ポリケタイド合成酵素 |
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| Outline of Final Research Achievements |
Acyltransferases (ATs) are key determinants of building block specificity in polyketide biosynthesis. Despite the importance of protein-protein interactions between AT and carrier protein (CP) during the acyltransfer reaction, the mechanism of CP recognition by AT had been poorly understood. In this study, we chemically synthesized pantetheineamide-type cross-linking probe to capture transient AT-CP complex in its functional state, and successfully determined the crystal structure of AT-CP complex of disorazole polyketide synthase (PKS). The crystal structure of the disorazole AT-CP complex provides the first detailed insights into the protein-protein interactions between a trans-acting AT and CP in trans-AT PKS assembly lines. We also showed that the pantetheineamide-type cross-linking probe is useful for structural characterization of adenylation domain-CP complexes.
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| Academic Significance and Societal Importance of the Research Achievements |
ポリケタイド化合物の生合成において、アシル基転移酵素はポリケタイド骨格の構成単位となるアシル基の種類を決定づける重要な酵素である。本研究では、ポリケタイド合成酵素におけるアシル基転移酵素とキャリアータンパク質の間のタンパク質間相互作用の詳細を明らかにすることに成功した。得られた構造情報を利用することにより、非天然型ポリケタイド化合物の微生物生産を目的とした合理的なポリケタイド合成酵素の改変が期待できる。
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Report
(5 results)
Research Products
(16 results)
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[Journal Article] An Engineered Aryl Acid Adenylation Domain with an Enlarged Substrate Binding Pocket2019
Author(s)
Ishikawa, F., Miyanaga, A., Kitayama, H., Nakamura, S., Nakanishi, I., Kudo, F., Eguchi, T., Tanabe, G.
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Journal Title
Angew. Chem. Int. Ed.
Volume: 58
Issue: 21
Pages: 6906-6910
DOI
Related Report
Peer Reviewed
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