Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Allosteric role of a structural NADP molecule in glucose-6-phosphate dehydrogenase activity.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 119, Issue 29, Page e2119695119, Year 2022
Publish date	Jul 19, 2022
Authors	Xuepeng Wei / Kathryn Kixmoeller / Elana Baltrusaitis / Xiaolu Yang / Ronen Marmorstein /
PubMed 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.
External links	Proc Natl Acad Sci U S A / PubMed:35858355 / PubMed Central
Methods	EM (single particle)
Resolution	2.2 - 3.7 Å
Structure data	25224 7snf EMDB-25224, PDB-7snf: Structure of G6PD-WT dimer Method: EM (single particle) / Resolution: 3.5 Å 25225 7sng EMDB-25225, PDB-7sng: structure of G6PD-WT tetramer Method: EM (single particle) / Resolution: 2.8 Å 25226 7snh EMDB-25226, PDB-7snh: Structure of G6PD-D200N tetramer bound to NADP+ Method: EM (single particle) / Resolution: 2.2 Å 25227 7sni EMDB-25227, PDB-7sni: Structure of G6PD-D200N tetramer bound to NADP+ and G6P Method: EM (single particle) / Resolution: 2.5 Å 26030 7toe EMDB-26030, PDB-7toe: Structure of G6PD-WT tetramer with no symmetry imposed Method: EM (single particle) / Resolution: 3.0 Å 26031 7tof EMDB-26031, PDB-7tof: Structure of G6PD-WT dimer with no symmetry applied Method: EM (single particle) / Resolution: 3.7 Å 26428 7ual EMDB-26428, PDB-7ual: Structure of G6PD-D200N tetramer bound to NADP+ and G6P with no symmetry applied Method: EM (single particle) / Resolution: 2.9 Å 26442 7uc2 EMDB-26442, PDB-7uc2: Structure of G6PD-D200N tetramer bound to NADP+ with no symmetry applied Method: EM (single particle) / Resolution: 2.5 Å
Chemicals	ChemComp-HOH: WATER ChemComp-NAP: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE ChemComp-BG6: 6-O-phosphono-beta-D-glucopyranose
Source	homo sapiens (human)
Keywords	OXIDOREDUCTASE / dehydrogenase / apo protein / D200N mutant / Glucose-6-phosphate 1-dehydrogenase