Structural identification and comprehension of human ALDH1L1-Gossypol complex.

Han, Chang Woo; Lee, Han Na; Jeong, Mi Suk; Kim, Hong Yeoul; Jang, Se Bok

Han, Chang Woo; Lee, Han Na; Jeong, Mi Suk; Kim, Hong Yeoul; Jang, Se Bok.

Afiliación

Han CW; Institute of Systems Biology, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan, 46241, Republic of Korea.
Lee HN; Department of Molecular Biology, College of Natural Sciences, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea.
Jeong MS; Institute of Systems Biology, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan, 46241, Republic of Korea.
Kim HY; Elysiumbio Inc #2007, Samsung Cheil B/D, 309 Teheran-ro, Gangnam-gu, Seoul, 06151, Republic of Korea.
Jang SB; Department of Molecular Biology, College of Natural Sciences, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea. Electronic address: sbjang@pusan.ac.kr.

Biochem Biophys Res Commun ; 726: 150306, 2024 09 24.

Article en En | MEDLINE | ID: mdl-38917634

ABSTRACT

ABSTRACT

The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric site and disrupts the folate metabolism by preventing NADP+ binding. The Cryo-EM structures of tetrameric C-terminal aldehyde dehydrogenase human ALDH1L1 complex with gossypol were examined. Gossypol-bound ALDH1L1 interfered with NADP+ by shifting the allosteric site of the structural conformation, producing a closed-form NADP+ binding site. In addition, the inhibition activity of ALDH1L1 was targeted with gossypol in NSCLC. The gossypol treatment had anti-cancer effects on NSCLC by blocking NADPH and ATP production. These findings emphasize the structure characterizing ALDH1L1 with gossypol.

Asunto(s)

Gosipol; Humanos; Gosipol/química; Gosipol/farmacología; Gosipol/metabolismo; NADP/metabolismo; NADP/química; Modelos Moleculares; Microscopía por Crioelectrón; Carcinoma de Pulmón de Células no Pequeñas/metabolismo; Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico; Carcinoma de Pulmón de Células no Pequeñas/patología; Neoplasias Pulmonares/metabolismo; Neoplasias Pulmonares/tratamiento farmacológico; Neoplasias Pulmonares/patología; Aldehído Oxidorreductasas/metabolismo; Aldehído Oxidorreductasas/química; Unión Proteica; Sitios de Unión; Sitio Alostérico; Conformación Proteica; Línea Celular Tumoral; Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH

Palabras clave

Cell metabolism; Cryo-electron microscopy; Gossypol; hALDH1L1

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Gosipol Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

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