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TitleStructure of putative tumor suppressor ALDH1L1.
Journal, issue, pagesCommun Biol, Vol. 5, Issue 1, Page 3, Year 2022
Publish dateJan 10, 2022
AuthorsYaroslav Tsybovsky / Valentin Sereda / Marcin Golczak / Natalia I Krupenko / Sergey A Krupenko /
PubMed AbstractPutative tumor suppressor ALDH1L1, the product of natural fusion of three unrelated genes, regulates folate metabolism by catalyzing NADP-dependent conversion of 10-formyltetrahydrofolate to ...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 CO. 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 CO, 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.
External linksCommun Biol / PubMed:35013550 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.7 Å
Structure data

EMDB-24540, PDB-7rlt:
Structure of ligand-free ALDH1L1 (10-formyltetrahydrofolate dehydrogenase)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-24547, PDB-7rlu:
Structure of ALDH1L1 (10-formyltetrahydrofolate dehydrogenase) in complex with NADP
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-PNS:
4'-PHOSPHOPANTETHEINE

ChemComp-NAP:
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

ChemComp-HOH:
WATER

Source
  • rattus norvegicus (Norway rat)
KeywordsCYTOSOLIC PROTEIN / folate metabolism / acyl carrier protein / peptidyl carrier protein

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