{{Sandbox_ESBS_2019}}
==Glucose-6-Phosphate Dehydrogenase from Leuconostoc ''mesenteroides''==
<StructureSection load='1dpg' size='340' side='right' caption='Caption for this structure' scene=''>
The protein''' Glucose-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.

See : [[G6PD(Hebrew)]]in Hebrew
== Function ==
'''G6PD''' plays an important role in the metabolism of L.''mesenteroides''.
L.''mesenteroides'' is a facultactively anaerobic micro-organism which metabolizes glucose to generate lactic acid, ethanol but also carbon dioxyde.
This glucose metabolic process (glycolysis and pentose phosphate pathway) is catalysed by '''G6PD'''. During this process, [[NADH]] is synthesised and used in the heterolactic fermentation and the biosynthesis of fatty acids.
The protein '''G6PD''' 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 <ref>PMID: 20608171</ref>.

== Genomic context ==
It is coded by the '''G6PD''' gene (1461 nucleotides)<ref>GeneID:29577449</ref>.
It has in total 2 chains. In the link below, these two chains are represented by one unique sequence entity.

External resource : click on [https://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=1DPG] to see the graphical representation on the RCSB website.

== Catalytic activity ==
'''D-glucose 6-phosphate + NAD+ → 6-phospho-D-glucono-1,5-lactone + H+ + NADH'''<ref>PMID: 9485426</ref>

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<ref>PMID: 12033926</ref>.

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.
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
<jmolCheckbox>
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dp/1dpg_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB].
<div style="clear:both"></div>

== 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<ref>PMID: 11106479</ref>:

MVSEIKTLVT FFGG '''T''' GDLAK R '''TK''' LYPSVFNL YKKGYLQKHF AIVGTA '''RQ''' AL NDDEFKQLVR DSIKDFTDDQ AQAEAFIEHF SYRAHDVTDA ASYAVLKEAI EEAADKFDID GNRIFYMSVA PRFFGTIAKY LKSEGLLADT GYNRLMIEK '''P''' FGTSYDTAAE LQNDLENAFD DNQLFRI '''DHY''' 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 ==
Glucose-6-Phosphate Dehydrogenase is formed of a homodimer, so a dimer of two identical [https://en.wikipedia.org/wiki/Protein_subunit subunit].

'''Secondary structure'''
A subunit contains 485 residues where 285 residues are in secondary structure. 93 residues are involved in 15 β-sheet strands and 192 in 17 helices.

'''Tertiary structure'''
Each <scene name='82/829347/Monomerg6pd/1'>monomer</scene> is composed of 2 domains, <scene name='82/829347/Homodimer_g6pd/5'>1 red and 1 green</scene>.
Depending on several conditions, it can dimerize to form tetramers. Each monomer is composed of a small domain localized in the amino terminal part which constitute the coenzyme binding domain and a larger domain in the carboxy terminal part which constitute the substrate binding domain. the complex has a substrate binding site that binds to G6P, and a catalytic coenzyme binding site that binds to NADP+ using the Rossman fold.<ref name="struc">PMID: 7881907</ref>

''Coenzyme binding domain''
The coenzyme binding domain binds the [[NAD]] or [[NADP]] which participes in the dehydrogenation of '''G6P'''.
It is defined by a typical [https://scop.berkeley.edu/sunid=30074 β-α-β dinucleotide-binding fold] corresponding to a [https://en.wikipedia.org/wiki/Rossmann_fold Rossman fold].

</StructureSection>
== References ==
<references/>

== Proteopedia page contributors and editors ==
DONATI Quentin, LOGEREAU Lucie, PROST Loana

2020-01-15T10:46:24Z

Lucie Logereau:

{{Sandbox_ESBS_2019}}
==Glucose-6-Phosphate Dehydrogenase from Leuconostoc ''mesenteroides''==
<StructureSection load='1dpg' size='340' side='right' caption='Caption for this structure' scene=''>
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 <ref>PMID: 20608171</ref>.

== Genomic context ==
It is coded by the G6PD gene (1461 nucleotides)<ref>GeneID:29577449</ref>.

== Catalytic activity ==
D-glucose 6-phosphate + NAD+ → 6-phospho-D-glucono-1,5-lactone + H+ + NADH<ref>PMID: 9485426</ref>

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<ref>PMID: 12033926</ref>.

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.
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
<jmolCheckbox>
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dp/1dpg_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB].
<div style="clear:both"></div>

== 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<ref>PMID: 11106479</ref>:

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<ref>PMID: 7881907</ref>. Each monomer is composed of 2 domains, <scene name='82/829347/Homodimer_g6pd/1'>1 red and 1 green.</scene>
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 <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.

</StructureSection>
== References ==
<references/>

== Proteopedia page contributors and editors ==
DONATI Quentin, LOGEREAU Lucie, PROST Loana