Sandbox Reserved 1094: Difference between revisions

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== 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>.

Each monomer is composed of a small domain localized in the amino terminal part (residues 1-177) which constitute the coenzyme binding domain and a larger domain in the ~~carboxy~~ terminal part (residues 178-485) ~~which constitute the substrate binding domain~~.<ref name="struc">PMID: 7881907</ref>

Each monomer is composed of a small domain localized in the amino terminal part (residues 1-177) which constitute the coenzyme binding domain and a larger domain in the carboxyl terminal part (residues 178-485).<ref name="struc">PMID: 7881907</ref>

*''Coenzyme binding domain''

The coenzyme binding domain binds the [https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NAD] or [https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide_phosphate 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].

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*''~~Substrate binding~~ domain''

*''Carboxyl terminus domain''

The ~~substrate binding~~ domain ~~binds to the 6-phosphate of '''G6P'''. It~~ is defined by a β+α particular fold which has created his own fold family the [https://scop.berkeley.edu/sunid=39989 G6PD-like]. It is composed of a large essentially antiparallel curved nine-stranded β-sheet with 11 helices.

The carboxyl terminus domain is defined by a β+α particular fold which has created his own fold family the [https://scop.berkeley.edu/sunid=39989 G6PD-like]. It is composed of a large essentially antiparallel curved nine-stranded β-sheet with 11 helices and remain well ordered to the carboxy-terminal residue. It is essential in the activity of the enzyme because it ensure the formation of the tertiary and the quaternary structure.

*''Domain boundary''

At the boundary between the two domains some helices of the ~~substrate binding~~ domain with multiples β strands and helices of the coenzyme binding domain ensuring the cohesion of the enzyme monomer.

At the boundary between the two domains some helices of the carboxy terminus domain interacts with multiples β strands and helices of the coenzyme binding domain ensuring the cohesion of the enzyme monomer.

There is a pocket where the phosphate of the substrate binds. Residues involved in the contact with the phosphate are His178, Glu147, Lys 148, Tyr 415 and Ile176.

Asp177 and His240 are two basic residues conserved and localized in the binding pocket which could act as base for the deshydrogenation reaction. Site-directed mutagenesis has shown that H240N mutant have a lower activity than the wild-type enzyme. So it has been deduced that His240 is involved as the base of the reaction.

'''Quaternary structure'''

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The dimer is very extend compared to the monomer with a size of 112Å.

The enzyme is found into a dimeric form in vivo. The two subunits interface is made by the contact between the two antiparallels β-sheets of the ~~substrate binding domains~~. Their interaction is crucial and form a β-half-barrel ([https://en.wikipedia.org/wiki/Beta_barrel β-Barrel ]) on one side of the protein which is closed on the other side by helices of each monomer. The majority of dimer contacts are hydrophobic with hydrophobic residues in the inside of the β-half-barrel but there are three salt bridges, especially a conserved one between Glu183 and Lys386 ; Lys 32 with Asp 390 and Arg395 with Asp 407, and two main chain hydrogen bonds which participates to the cohesion of the structure. Glu183 is the last residue of the nine-residue conserved peptide.

The enzyme is found into a dimeric form in vivo. The two subunits interface is made by the contact between the two antiparallels β-sheets of the carboxyl terminus domain. Their interaction is crucial and form a β-half-barrel ([https://en.wikipedia.org/wiki/Beta_barrel β-Barrel ]) on one side of the protein which is closed on the other side by helices of each monomer. The majority of dimer contacts are hydrophobic with hydrophobic residues in the inside of the β-half-barrel but there are three salt bridges, especially a conserved one between Glu183 and Lys386 ; Lys 32 with Asp 390 and Arg395 with Asp 407, and two main chain hydrogen bonds which participates to the cohesion of the structure. Glu183 is the last residue of the nine-residue conserved peptide.

The active site of the enzyme is contained in each monomer but the dimeric form is necessary to the biological activity indeed it confers the stability in aqueous medium.

Sandbox Reserved 1094: Difference between revisions

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@@ Line 51: / Line 51: @@
 == 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>.
-Each monomer is composed of a small domain localized in the amino terminal part (residues 1-177) which constitute the coenzyme binding domain and a larger domain in the carboxy terminal part (residues 178-485) which constitute the substrate binding domain.<ref name="struc">PMID: 7881907</ref>
+Each monomer is composed of a small domain localized in the amino terminal part (residues 1-177) which constitute the coenzyme binding domain and a larger domain in the carboxyl terminal part (residues 178-485).<ref name="struc">PMID: 7881907</ref>
 *''Coenzyme binding domain''
 The coenzyme binding domain binds the [https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide NAD]  or [https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide_phosphate 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].
@@ Line 67: / Line 71: @@
-*''Substrate binding domain''
+*''Carboxyl terminus domain''
-The substrate binding domain binds to the 6-phosphate of '''G6P'''. It is defined by a β+α particular fold which has created his own fold family the [https://scop.berkeley.edu/sunid=39989 G6PD-like]. It is composed of a large essentially antiparallel curved nine-stranded β-sheet with 11 helices.
+The carboxyl terminus domain is defined by a β+α particular fold which has created his own fold family the [https://scop.berkeley.edu/sunid=39989 G6PD-like]. It is composed of a large essentially antiparallel curved nine-stranded β-sheet with 11 helices and remain well ordered to the carboxy-terminal residue. It is essential in the activity of the enzyme because it ensure the formation of the tertiary and the quaternary structure.
 *''Domain boundary''
-At the boundary between the two domains some helices of the substrate binding domain with multiples β strands and helices of the coenzyme binding domain ensuring the cohesion of the enzyme monomer.
+At the boundary between the two domains some helices of the carboxy terminus domain interacts with multiples β strands and helices of the coenzyme binding domain ensuring the cohesion of the enzyme monomer.
 There is a pocket where the phosphate of the substrate binds. Residues involved in the contact with the phosphate are His178, Glu147, Lys 148, Tyr 415 and Ile176.
+Asp177 and His240 are two basic residues conserved and localized in the binding pocket which could act as base for the deshydrogenation reaction. Site-directed mutagenesis has shown that H240N mutant have a lower activity than the wild-type enzyme. So it has been deduced that His240 is involved as the base of the reaction.
 '''Quaternary structure'''
@@ Line 81: / Line 89: @@
 The dimer is very extend compared to the monomer with a size of 112Å.
-The enzyme is found into a dimeric form in vivo. The two subunits interface is made by the contact between the two antiparallels β-sheets of the substrate binding domains. Their interaction is crucial and form a β-half-barrel ([https://en.wikipedia.org/wiki/Beta_barrel β-Barrel ]) on one side of the protein which is closed on the other side by helices of each monomer. The majority of dimer contacts are hydrophobic with hydrophobic residues in the inside of the β-half-barrel but there are three salt bridges, especially a conserved one between Glu183 and Lys386 ; Lys 32 with Asp 390 and Arg395 with Asp 407, and two main chain hydrogen bonds which participates to the cohesion of the structure. Glu183 is the last residue of the nine-residue conserved peptide.
+The enzyme is found into a dimeric form in vivo. The two subunits interface is made by the contact between the two antiparallels β-sheets of the carboxyl terminus domain. Their interaction is crucial and form a β-half-barrel ([https://en.wikipedia.org/wiki/Beta_barrel β-Barrel ]) on one side of the protein which is closed on the other side by helices of each monomer. The majority of dimer contacts are hydrophobic with hydrophobic residues in the inside of the β-half-barrel but there are three salt bridges, especially a conserved one between Glu183 and Lys386 ; Lys 32 with Asp 390 and Arg395 with Asp 407, and two main chain hydrogen bonds which participates to the cohesion of the structure. Glu183 is the last residue of the nine-residue conserved peptide.
 The active site of the enzyme is contained in each monomer but the dimeric form is necessary to the biological activity indeed it confers the stability in aqueous medium.