This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115.
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It is involved in the processing of carbohydrates as it has important roles in the glucose metabolic process (glycolysis and pentose phosphate pathway).
It also has a role in protecting cells from destruction because it produces a cofactor NADPH which plays a role in protecting cells from reactive oxygen species.
Genomic context
It is coded by the G6PD gene (1461 nucleotides).
Catalytic activity
D-glucose 6-phosphate + NAD+ → 6-phospho-D-glucono-1,5-lactone + H+ + NADH
KM=114 µM for G6PD (with NADP), KM=69 µM for G6PD (with NAD),
KM=8.0 µM for NADP, KM=160 µM for NAD
Its regulation depends on the concentration of substrate and coenzyme, rate limiting step in pentose phosphate pathway.
Optimal activity conditions
Optimum pH is 5.4 - 8.9.
Evolutionary conservation
We will keep the interactivity that exist on the page: a box can be checked to observe the different structures conserved evolutionary.
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Mutations
Mutagenesis inducing catalytic activity loss: +200 mutations have been identified. A change of amino acids leads to disruption of the normal
structure/function/reduce the expression of enzymes.
Structural highlights
It is formed of a homodimer (dimer of two identical monomers).
Depending on several conditions, it can dimerize to form tetramers. Each monomer in the complex has a substrate binding site that binds to G6P, and a catalytic coenzyme binding site that binds to NADP+/NADPH using the Rossman fold.
This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
↑Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:https://dx.doi.org/10.1002/ijch.201300024
↑Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
References
Ravera S., Calzia D., Morelli A. et Panfoli I. 2010. Oligomerization studies of Leuconostoc mesenteroides G6PD activity after SDS-PAGE and blotting. Molekuliarnaia Biologiia. 44(3):472-6.
Cosgrove MS., Naylor C., Paludan S., Adams MJ. et Levy HR. 1998. On the mechanism of the reaction catalyzed by glucose 6-phosphate dehydrogenase. Biochemistry. 37(9):2759-67.
Cosgrove MS., Loh SN., Ha JH. et Levy HR. 2002. The catalytic mechanism of glucose 6-phosphate dehydrogenases: assignment and 1H NMR spectroscopy pH titration of the catalytic histidine residue in the 109 kDa Leuconostoc mesenteroides enzyme. Biochemistry. 41(22):6939-45.
Rowland P, Basak AK, Gover S, Levy HR, Adams MJ. The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc
mesenteroides refined at 2.0 A resolution. Structure. 1994 Nov 15;2(11):1073-87.