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Structure of putative tumor suppressor ALDH1L1.
Tsybovsky, Yaroslav; Sereda, Valentin; Golczak, Marcin; Krupenko, Natalia I; Krupenko, Sergey A.
Afiliación
  • Tsybovsky Y; Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 8560 Progress Drive, Frederick, MD, 21701, USA. Yaroslav.Tsybovsky@nih.gov.
  • Sereda V; Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
  • Golczak M; Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USA.
  • Krupenko NI; Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
  • Krupenko SA; Department of Nutrition, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, NC, 27599, USA.
Commun Biol ; 5(1): 3, 2022 01 10.
Article en En | MEDLINE | ID: mdl-35013550
Putative tumor suppressor ALDH1L1, the product of natural fusion of three unrelated genes, regulates folate metabolism by catalyzing NADP+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Cryo-EM structures of tetrameric rat ALDH1L1 revealed the architecture and functional domain interactions of this complex enzyme. Highly mobile N-terminal domains, which remove formyl from 10-formyltetrahydrofolate, undergo multiple transient inter-domain interactions. The C-terminal aldehyde dehydrogenase domains, which convert formyl to CO2, form unusually large interfaces with the intermediate domains, homologs of acyl/peptidyl carrier proteins (A/PCPs), which transfer the formyl group between the catalytic domains. The 4'-phosphopantetheine arm of the intermediate domain is fully extended and reaches deep into the catalytic pocket of the C-terminal domain. Remarkably, the tetrameric state of ALDH1L1 is indispensable for catalysis because the intermediate domain transfers formyl between the catalytic domains of different protomers. These findings emphasize the versatility of A/PCPs in complex, highly dynamic enzymatic systems.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genes Supresores de Tumor / Proteínas Supresoras de Tumor / Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH Límite: Animals Idioma: En Revista: Commun Biol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genes Supresores de Tumor / Proteínas Supresoras de Tumor / Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH Límite: Animals Idioma: En Revista: Commun Biol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido