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Geldanamycin and its derivatives, inhibitors of heat shock protein 90, are considered potent anticancer drugs, although their biosynthetic pathways have not yet been fully elucidated. The key step of conversion of 4,5-dihydrogeldanamycin to geldanamycin was expected to catalyze by a P450 monooxygenase, Gel16. The adequate bioconversions by cytochrome P450 mostly rely upon its interaction with redox partners. Several ferredoxin and ferredoxin reductases are available in the genome of certain organisms, but only a few suitable partners can operate in full efficiency. In this study, we have expressed cytochrome P450 gel16 in Escherichia coli and performed an in vitro assay using 4,5-dihydrogeldanamycin as a substrate. We demonstrated that the in silico method can be applicable for the efficient mining of convenient endogenous redox partners (9 ferredoxins and 6 ferredoxin reductases) against CYP Gel16 from Streptomyces hygroscopicus. The distances for ligand FDX4-FDR6 were found to be 9.384 Å.

Similarly, the binding energy between Gel16-FDX4 and FDX4-FDR6 were -611.88 kcal/mol and -834.48 kcal/mol, respectively, suggesting the lowest distance and binding energy rather than other redox partners. These findings suggest that the best redox partners of Gel16 could be NADPH → FDR6 → FDX4 → Gel16.

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기사명 저자명 페이지 원문 목차
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Development of an RNA expression platform controlled by viral internal ribosome entry sites Hae Li Ko, Hyo-Jung Park, Jihye Kim, Ha Kim, Hyewon Youn, Jae-Hwan Nam p.127-140

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A role of YlBud8 in the regulation of cell separation in the yeast Yarrowia lipolytica Yun-Qing Li, Qing-Jie Xue, Yuan-Yuan Yang, Hui Wang, Xiu-Zhen Li p.141-150

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Lipoteichoic acid isolated from Lactobacillus plantarum maintains inflammatory homeostasis through regulation of Th1- and Th2- induced cytokines Ji Eun Ahn, Hangeun Kim, Dae Kyun Chung p.151-159

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Gold nanoparticles conjugation enhances antiacanthamoebic properties of nystatin, fluconazole and amphotericin B Ayaz Anwar, Ruqaiyyah Siddiqui, Muhammad Raza Shah, Naveed Ahmed Khan p.171-177

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Zinc ions affect siderophore production by fungi isolated from the Panax ginseng rhizosphere Khalid Abdallah Hussein, Jin Ho Joo p.105-113

참고문헌 (41건) : 자료제공( 네이버학술정보 )

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번호 참고문헌 국회도서관 소장유무
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