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- PDB-7yjj: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossy... -

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Basic information

Entry
Database: PDB / ID: 7yjj
TitleHuman Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossypol complex
ComponentsCytosolic 10-formyltetrahydrofolate dehydrogenase
KeywordsOXIDOREDUCTASE / Cytosolic 10-formyltetrahydrofolate dehydrogenase / Aldehyde dehydrogenase family 1 member L1 / inhibitor / Gossypol
Function / homology
Function and homology information


formyltetrahydrofolate dehydrogenase / formyltetrahydrofolate dehydrogenase activity / 10-formyltetrahydrofolate catabolic process / NADPH regeneration / Metabolism of folate and pterines / aldehyde dehydrogenase (NAD+) activity / biosynthetic process / tetrahydrofolate interconversion / mitochondrion / extracellular exosome / cytosol
Similarity search - Function
10-formyltetrahydrofolate dehydrogenase / Formyl transferase, C-terminal domain superfamily / Formyl transferase, C-terminal / Formyl transferase, C-terminal domain / Formyl transferase-like, C-terminal domain superfamily / Phosphoribosylglycinamide formyltransferase, active site / Phosphoribosylglycinamide formyltransferase active site. / Formyl transferase, N-terminal / Formyl transferase / Formyl transferase, N-terminal domain superfamily ...10-formyltetrahydrofolate dehydrogenase / Formyl transferase, C-terminal domain superfamily / Formyl transferase, C-terminal / Formyl transferase, C-terminal domain / Formyl transferase-like, C-terminal domain superfamily / Phosphoribosylglycinamide formyltransferase, active site / Phosphoribosylglycinamide formyltransferase active site. / Formyl transferase, N-terminal / Formyl transferase / Formyl transferase, N-terminal domain superfamily / Aldehyde dehydrogenase, glutamic acid active site / Aldehyde dehydrogenases glutamic acid active site. / Aldehyde dehydrogenase, cysteine active site / Aldehyde dehydrogenases cysteine active site. / Aldehyde dehydrogenase domain / Aldehyde dehydrogenase family / Aldehyde dehydrogenase, C-terminal / Aldehyde dehydrogenase, N-terminal / Aldehyde/histidinol dehydrogenase / Phosphopantetheine attachment site / ACP-like superfamily / Carrier protein (CP) domain profile. / Phosphopantetheine binding ACP domain
Similarity search - Domain/homology
Gossypol / Cytosolic 10-formyltetrahydrofolate dehydrogenase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.31 Å
AuthorsHan, C.W. / Lee, H.N. / Jeong, M.S. / Jang, S.B.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Biochem Biophys Res Commun / Year: 2024
Title: Structural identification and comprehension of human ALDH1L1-Gossypol complex.
Authors: Chang Woo Han / Han Na Lee / Mi Suk Jeong / Hong Yeoul Kim / Se Bok Jang /
Abstract: The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric ...The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO. 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.
History
DepositionJul 20, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 26, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 3, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond / em_admin / Item: _em_admin.last_update
Revision 1.2Aug 7, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: Cytosolic 10-formyltetrahydrofolate dehydrogenase
C: Cytosolic 10-formyltetrahydrofolate dehydrogenase
D: Cytosolic 10-formyltetrahydrofolate dehydrogenase
E: Cytosolic 10-formyltetrahydrofolate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)218,2765
Polymers217,7574
Non-polymers5191
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein
Cytosolic 10-formyltetrahydrofolate dehydrogenase / 10-FTHFDH / FDH / Aldehyde dehydrogenase family 1 member L1


Mass: 54439.246 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ALDH1L1, FTHFD / Production host: Escherichia coli (E. coli)
References: UniProt: O75891, formyltetrahydrofolate dehydrogenase
#2: Chemical ChemComp-GO3 / Gossypol


Mass: 518.554 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C30H30O8 / Comment: inhibitor*YM
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossypol complex
Type: COMPLEX
Details: Protein (Human Cytosolic 10-formyltetrahydrofolate dehydrogenase) and chemical (Gossypol) complex
Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.223 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: NITROGEN

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Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: DARK FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingAverage exposure time: 54.56 sec. / Electron dose: 39.55 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 6.31 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 396292 / Symmetry type: POINT
RefinementStereochemistry target values: CDL v1.2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.006615651
ELECTRON MICROSCOPYf_angle_d0.955321196
ELECTRON MICROSCOPYf_chiral_restr0.05152380
ELECTRON MICROSCOPYf_plane_restr0.0062748
ELECTRON MICROSCOPYf_dihedral_angle_d13.14959347

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