2bh9
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X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP
OverviewOverview
Human glucose-6-phosphate dehydrogenase (G6PD) is NADP(+)-dependent and, catalyses the first and rate-limiting step of the pentose phosphate shunt., Binary complexes of the human deletion mutant, DeltaG6PD, with, glucose-6-phosphate and NADP(+) have been crystallized and their, structures solved to 2.9 and 2.5 A, respectively. The structures are, compared with the previously determined structure of the Canton variant of, human G6PD (G6PD(Canton)) in which NADP(+) is bound at the structural, site. Substrate binding in DeltaG6PD is shown to be very similar to that, described previously in Leuconostoc mesenteroides G6PD. NADP(+) binding at, the coenzyme site is seen to be comparable to NADP(+) binding in L., mesenteroides G6PD, although some differences arise as a result of, sequence changes. The tetramer interface varies slightly among the human, G6PD complexes, suggesting flexibility in the predominantly hydrophilic, dimer-dimer interactions. In both complexes, Pro172 of the conserved, peptide EKPxG is in the cis conformation; it is seen to be crucial for, close approach of the substrate and coenzyme during the enzymatic, reaction. Structural NADP(+) binds in a very similar way in the, DeltaG6PD-NADP(+) complex and in G6PD(Canton), while in the substrate, complex the structural NADP(+) has low occupancy and the C-terminal tail, at the structural NADP(+) site is disordered. The implications of possible, interaction between the structural NADP(+) and G6P are considered.
DiseaseDisease
Known diseases associated with this structure: Favism OMIM:[305900], G6PD deficiency OMIM:[305900], Hemolytic anemia due to G6PD deficiency OMIM:[305900]
About this StructureAbout this Structure
2BH9 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Glucose-6-phosphate 1-dehydrogenase, with EC number 1.1.1.49 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase., Kotaka M, Gover S, Vandeputte-Rutten L, Au SW, Lam VM, Adams MJ, Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):495-504. Epub 2005, Apr 20. PMID:15858258
Page seeded by OCA on Sun Feb 3 10:24:01 2008