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Yorodumi- EMDB-33872: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossy... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33872 | |||||||||
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Title | Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossypol complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Cytosolic 10-formyltetrahydrofolate dehydrogenase / Aldehyde dehydrogenase family 1 member L1 / inhibitor / Gossypol / OXIDOREDUCTASE | |||||||||
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 / one-carbon metabolic process / extracellular exosome / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.31 Å | |||||||||
Authors | Han CW / Lee HN / Jeong MS / Jang SB | |||||||||
Funding support | 1 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33872.map.gz | 59.7 MB | EMDB map data format | |
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Header (meta data) | emd-33872-v30.xml emd-33872.xml | 16.3 KB 16.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33872_fsc.xml | 11.7 KB | Display | FSC data file |
Images | emd_33872.png | 30.2 KB | ||
Filedesc metadata | emd-33872.cif.gz | 5.5 KB | ||
Others | emd_33872_additional_1.map.gz emd_33872_half_map_1.map.gz emd_33872_half_map_2.map.gz | 60.3 MB 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33872 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33872 | HTTPS FTP |
-Related structure data
Related structure data | 7yjjMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33872.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.9663 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_33872_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33872_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33872_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossy...
Entire | Name: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossypol complex |
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Components |
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-Supramolecule #1: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossy...
Supramolecule | Name: Human Cytosolic 10-formyltetrahydrofolate dehydrogenase and Gossypol complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Protein (Human Cytosolic 10-formyltetrahydrofolate dehydrogenase) and chemical (Gossypol) complex |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 223 KDa |
-Macromolecule #1: Cytosolic 10-formyltetrahydrofolate dehydrogenase
Macromolecule | Name: Cytosolic 10-formyltetrahydrofolate dehydrogenase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: formyltetrahydrofolate dehydrogenase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 54.439246 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: SIDYVEMAVN KRTVRMPHQL FIGGEFVDAE GAKTSETINP TDGSVICQVS LAQVTDVDKA VAAAKDAFEN GRWGKISARD RGRLMYRLA DLMEQHQEEL ATIEALDAGA VYTLALKTHV GMSIQTFRYF AGWCDKIQGS TIPINQARPN RNLTLTRKEP V GVCGIIIP ...String: SIDYVEMAVN KRTVRMPHQL FIGGEFVDAE GAKTSETINP TDGSVICQVS LAQVTDVDKA VAAAKDAFEN GRWGKISARD RGRLMYRLA DLMEQHQEEL ATIEALDAGA VYTLALKTHV GMSIQTFRYF AGWCDKIQGS TIPINQARPN RNLTLTRKEP V GVCGIIIP WNYPLMMLSW KTAACLAAGN TVVIKPAQVT PLTALKFAEL TLKAGIPKGV VNVLPGSGSL VGQRLSDHPD VR KIGFTGS TEVGKHIMKS CAISNVKKVS LELGGKSPLI IFADCDLNKA VQMGMSSVFF NKGENCIAAG RLFVEDSIHD EFV RRVVEE VRKMKVGNPL DRDTDHGPQN HHAHLVKLME YCQHGVKEGA TLVCGGNQVP RPGFFFEPTV FTDVEDHMFI AKEE SFGPV MIISRFADGD LDAVLSRANA TEFGLASGVF TRDINKALYV SDKLQAGTVF VNTYNKTDVA APFGGFKQSG FGKDL GEAA LNEYLRVKTV TFEY UniProtKB: Cytosolic 10-formyltetrahydrofolate dehydrogenase |
-Macromolecule #2: Gossypol
Macromolecule | Name: Gossypol / type: ligand / ID: 2 / Number of copies: 1 / Formula: GO3 |
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Molecular weight | Theoretical: 518.554 Da |
Chemical component information | ChemComp-GO3: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.8 |
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Vitrification | Cryogen name: NITROGEN |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average exposure time: 54.56 sec. / Average electron dose: 39.55 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |