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The protein Glycose-6-Phosphate Dehydrogenase is an enzyme involved in the metabolic pathways of the majority of organisms. Leuconostoc mesenteroides is a Bacilli Gram-positive bacterium that expresses this enzyme.

Function

The Glucose-6-Phosphate Dehydrogenase is involved in the processing of carbohydrates as it has important roles in the glucose metabolic process (glycolysis and pentose phosphate pathway). Leuconostoc mesenteroides is a facultactively anaerobic micro-organism which metabolizes glucose to generate lactic acid, ethanol but also carbon dioxyde. This reaction is catalysed by G6PD synthesised NADH ; NADH is used in this heterolactic fermentation and the biosynthesis of fatty acids. Thus, G6PD plays an essential, amphibolic role in the metabolism of L. mesenteroides.

The Glucose-6-Phosphate Dehydrogenase 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 as it produces the co-factor NADPH which plays a role in protecting cells from reactive oxygen species ^[1].

Genomic context

It is coded by the G6PD gene (1461 nucleotides)^[2].

Catalytic activity

D-glucose 6-phosphate + NAD+ → 6-phospho-D-glucono-1,5-lactone + H+ + NADH^[3]

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^[4].

Optimum pH for its activity is 5.4 - 8.9.

Evolutionary conservation

The different structures conserved evolutionary can be observed according to the scale following.

Check, as determined by ConSurfDB.

Mutations

Mutagenesis of this enzyme induces catalytic activity loss: more than 200 mutations have been identified. A mutation in a nucleotide in the sequence coding for G6PD leads to disruption of the normal expression of the enzyme, or to a disruption in the amino acid structure of the enzyme which leads to a loss or decrease of catalytic activity toward its substrate.

The most common mutations in the amino acids sequence found that induce a loss of catalytic activity are a substitution of the bold amino acids by another one^[5]:

MVSEIKTLVT FFGG T GDLAK R K LYPSVFNL YKKGYLQKHF AIVGTA R Q AL NDDEFKQLVR DSIKDFTDDQ AQAEAFIEHF SYRAHDVTDA ASYAVLKEAI EEAADKFDID GNRIFYMSVA PRFFGTIAKY LKSEGLLADT GYNRLMIEK P FGTSYDTAAE LQNDLENAFD DNQLFRI D H Y LG K EMVQNIA ALRFGNPIFD AAWNKDYIKN VQVTLSEVLG VEERAGYYDT AGALLDMIQN H TMQIVGWLA MEKPESFTDK DIRAAKNAAF NALKIYDEAE VNKYFVRAQY GAGDSADFKP YLEELDVPAD SKNNTFIAGE LQFDLPRWEG VPFYVRSGKR LAA K QTRVDI VFKAGTFNFG SEQEAQEAVL SIII D PKGAI ELKLNAKSVE DAFNTRTIDL GWTVSDEDKK NTPEP Y ERMI HDTMNGDGSN FADWNGVSIA WKFVDAISAV YTADKAPLET YKSGSMGPEA SDKLLAANGD AWVFKG.

This sequence being the normal protein sequence found in L. mesenteroides.

Structural highlights

It is formed of a homodimer, so a dimer of two identical monomers. Each is composed of 2 domains, 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.^[6]

This is a sample scene created with SAT to by Group, and another to make of the protein. ^[6]