2BHL

X-RAY STRUCTURE OF HUMAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE (DELETION VARIANT) COMPLEXED WITH GLUCOSE-6-PHOSPHATE

Summary for 2BHL

• Entry DOI: 10.2210/pdb2bhl/pdb
• Related: 1QKI 2BH9
• Descriptor: GLUCOSE-6-PHOSPHATE 1-DEHYDROGENASE, GLYCEROL, 6-O-phosphono-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: oxidoreductase, oxidoreductase (choh(d)-nadp), glucose metabolism
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 113867.35

Authors

Kotaka, M.,Gover, S.,Lam, V.M.S.,Adams, M.J. (deposition date: 2005-01-13, release date: 2005-04-25, Last modification date: 2023-12-13)

Primary citation

Kotaka, M.,Gover, S.,Vandeputte-Rutten, L.,Au, S.W.N.,Lam, V.M.S.,Adams, M.J.
Structural Studies of Glucose-6-Phosphate and Nadp+ Binding to Human Glucose-6-Phosphate Dehydrogenase
Acta Crystallogr.,Sect.D, 61:495-, 2005

PubMed Abstract: 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.

PubMed: 15858258
DOI: 10.1107/S0907444905002350

Experimental method

X-RAY DIFFRACTION (2.9 Å)