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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | structure of G6PD-WT tetramer | |||||||||
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![]() | apo protein / ![]() | |||||||||
Function / homology | ![]() negative regulation of protein glutathionylation / pentose biosynthetic process / ribose phosphate biosynthetic process / glucose-6-phosphate dehydrogenase (NADP+) / positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Wei X / Marmorstein R | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Allosteric role of a structural NADP molecule in glucose-6-phosphate dehydrogenase activity. Authors: Xuepeng Wei / Kathryn Kixmoeller / Elana Baltrusaitis / Xiaolu Yang / Ronen Marmorstein / ![]() Abstract: Human glucose-6-phosphate dehydrogenase (G6PD) is the main cellular source of NADPH, and thus plays a key role in maintaining reduced glutathione to protect cells from oxidative stress disorders such ...Human glucose-6-phosphate dehydrogenase (G6PD) is the main cellular source of NADPH, and thus plays a key role in maintaining reduced glutathione to protect cells from oxidative stress disorders such as hemolytic anemia. G6PD is a multimeric enzyme that uses the cofactors β-D-glucose 6-phosphate (G6P) and "catalytic" NADP (NADPc), as well as a "structural" NADP (NADPs) located ∼25 Å from the active site, to generate NADPH. While X-ray crystallographic and biochemical studies have revealed a role for NADPs in maintaining the catalytic activity by stabilizing the multimeric G6PD conformation, other potential roles for NADPs have not been evaluated. Here, we determined the high resolution cryo-electron microscopy structures of human wild-type G6PD in the absence of bound ligands and a catalytic G6PD-D200N mutant bound to NADPc and NADPs in the absence or presence of G6P. A comparison of these structures, together with previously reported structures, reveals that the unliganded human G6PD forms a mixture of dimers and tetramers with similar overall folds, and binding of NADPs induces a structural ordering of a C-terminal extension region and allosterically regulates G6P binding and catalysis. These studies have implications for understanding G6PD deficiencies and for therapy of G6PD-mediated disorders. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 20.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10 KB 10 KB | Display Display | ![]() |
Images | ![]() | 164.3 KB | ||
Filedesc metadata | ![]() | 5.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7sngMC ![]() 7snfC ![]() 7snhC ![]() 7sniC ![]() 7toeC ![]() 7tofC ![]() 7ualC ![]() 7uc2C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : G6PD protein
Entire | Name: G6PD protein![]() |
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Components |
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-Supramolecule #1: G6PD protein
Supramolecule | Name: G6PD protein / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 110 KDa |
-Macromolecule #1: Glucose-6-phosphate 1-dehydrogenase
Macromolecule | Name: Glucose-6-phosphate 1-dehydrogenase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: glucose-6-phosphate dehydrogenase (NADP+) |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 60.403754 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MAEQVALSRT QVCGILREEL FQGDAFHQSD THIFIIMGAS GDLAKKKIYP TIWWLFRDGL LPENTFIVGY ARSRLTVADI RKQSEPFFK ATPEEKLKLE DFFARNSYVA GQYDDAASYQ RLNSHMNALH LGSQANRLFY LALPPTVYEA VTKNIHESCM S QIGWNRII ...String: MAEQVALSRT QVCGILREEL FQGDAFHQSD THIFIIMGAS GDLAKKKIYP TIWWLFRDGL LPENTFIVGY ARSRLTVADI RKQSEPFFK ATPEEKLKLE DFFARNSYVA GQYDDAASYQ RLNSHMNALH LGSQANRLFY LALPPTVYEA VTKNIHESCM S QIGWNRII VEKPFGRDLQ SSDRLSNHIS SLFREDQIYR IDHYLGKEMV QNLMVLRFAN RIFGPIWNRD NIACVILTFK EP FGTEGRG GYFDEFGIIR DVMQNHLLQM LCLVAMEKPA STNSDDVRDE KVKVLKCISE VQANNVVLGQ YVGNPDGEGE ATK GYLDDP TVPRGSTTAT FAAVVLYVEN ERWDGVPFIL RCGKALNERK AEVRLQFHDV AGDIFHQQCK RNELVIRVQP NEAV YTKMM TKKPGMFFNP EESELDLTYG NRYKNVKLPD AYERLILDVF CGSQMHFVRS DELREAWRIF TPLLHQIELE KPKPI PYIY GSRGPTEADE LMKRVGFQYE GTYKWVNPHK LLEHHHHHH UniProtKB: Glucose-6-phosphate 1-dehydrogenase |
-Macromolecule #2: water
Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 104 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Applied symmetry - Point group: D2 (2x2 fold dihedral![]() |