Group:SMART:2010 Pingry SMART Team: Difference between revisions

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'''Design description'''

2,5-DKGR A ~~possesses~~ a parallel alpha-beta ~~structural motif~~ of eight <scene name='2010_Pingry_SMART_Team/1a80-default/2'>alpha helices(highlighted red) and eight beta strands(highlighted blue)</scene>~~found in~~ other enzymes of the aldo-keto reductase(AKR) family. Also conserved in members of the AKR family is the residue,<scene name='2010_Pingry_SMART_Team/1a80-original/10'>Tyr50</scene>, that functions as both the proton donor and part of the catalytic triad. The residues,<scene name='2010_Pingry_SMART_Team/1a80-original/7'>Ala47 and Trp77</scene>, are demonstrated in all AKR enzymes as well as contributors to the formation of the substrate binding pocket at the C-terminal side of the barrel. Located on an extended conformation from the outer edge of the barrel is the binding site on 2,5-DKGR A for the

The structure of 2,5-DKGR A is a parallel alpha-beta structure consisting of eight <scene name='2010_Pingry_SMART_Team/1a80-default/2'>alpha helices(highlighted red) and eight beta strands(highlighted blue)</scene>. The alpha-beta structural motif is common among other enzymes of the aldo-keto reductase(AKR) family. Also conserved in the members of the AKR family is the residue,<scene name='2010_Pingry_SMART_Team/1a80-original/10'>Tyr50</scene> that critically functions as both the proton donor and part of the catalytic triad. The residues,<scene name='2010_Pingry_SMART_Team/1a80-original/7'>Ala47 and Trp77</scene>, are demonstrated in all AKR enzymes as well as contributors to the formation of the substrate binding pocket at the C-terminal side of the barrel. Located on an extended conformation from the outer edge of the barrel is the binding site on 2,5-DKGR A for the

<scene name='2010_Pingry_SMART_Team/1a80-original/12'>NADPH cofactor(shown in wireframe and colored CPK)</scene>. The NADPH cofactor is stabilized through hydrogen bonds, ionic bonds, and an aromatic pi-stacking interaction between <scene name='2010_Pingry_SMART_Team/1a80-original/2'>Trp187</scene> and the nicotinamide ring of NADPH . Although 2,5-DKGR A functions with NADPH as a cofactor, NADH is preferred for a more efficient production of vitamin C. To achieve this, mutations of the original side chains of <scene name='2010_Pingry_SMART_Team/1a80-default/1'>Lys232, Phe22, Arg238, and Ala272</scene> were conducted. Significantly, the <scene name='2010_Pingry_SMART_Team/1a80-original/8'>Lys232, Ser233, and Val234</scene> sidechain interact with the phosphate group of NADPH. In order to acommodate for the cofactor, NADH, and the absent phosphate group, these side chains have been modified in the mutant form.

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 '''Design description'''
-,5-DKGR A possesses a parallel alpha-beta structural motif of eight <scene name='2010_Pingry_SMART_Team/1a80-default/2'>alpha helices(highlighted red) and eight beta strands(highlighted blue)</scene>found in other enzymes of the aldo-keto reductase(AKR) family. Also conserved in members of the AKR family is the residue,<scene name='2010_Pingry_SMART_Team/1a80-original/10'>Tyr50</scene>, that functions as both the proton donor and part of the catalytic triad. The residues,<scene name='2010_Pingry_SMART_Team/1a80-original/7'>Ala47 and Trp77</scene>, are demonstrated in all AKR enzymes as well as contributors to the formation of the substrate binding pocket at the C-terminal side of the barrel. Located on an extended conformation from the outer edge of the barrel is the binding site on 2,5-DKGR A for the
+The structure of 2,5-DKGR A is a parallel alpha-beta structure consisting of eight <scene name='2010_Pingry_SMART_Team/1a80-default/2'>alpha helices(highlighted red) and eight beta strands(highlighted blue)</scene>. The alpha-beta structural motif is common among other enzymes of the aldo-keto reductase(AKR) family. Also conserved in the members of the AKR family is the residue,<scene name='2010_Pingry_SMART_Team/1a80-original/10'>Tyr50</scene> that critically functions as both the proton donor and part of the catalytic triad. The residues,<scene name='2010_Pingry_SMART_Team/1a80-original/7'>Ala47 and Trp77</scene>, are demonstrated in all AKR enzymes as well as contributors to the formation of the substrate binding pocket at the C-terminal side of the barrel. Located on an extended conformation from the outer edge of the barrel is the binding site on 2,5-DKGR A for the
 <scene name='2010_Pingry_SMART_Team/1a80-original/12'>NADPH cofactor(shown in wireframe and colored CPK)</scene>. The NADPH cofactor is stabilized through hydrogen bonds, ionic bonds, and an aromatic pi-stacking interaction between <scene name='2010_Pingry_SMART_Team/1a80-original/2'>Trp187</scene> and the nicotinamide ring of NADPH . Although 2,5-DKGR A functions with NADPH as a cofactor, NADH is preferred for a more efficient production of vitamin C. To achieve this, mutations of the original side chains of <scene name='2010_Pingry_SMART_Team/1a80-default/1'>Lys232, Phe22, Arg238, and Ala272</scene> were conducted. Significantly, the <scene name='2010_Pingry_SMART_Team/1a80-original/8'>Lys232, Ser233, and Val234</scene> sidechain interact with the phosphate group of NADPH. In order to acommodate for the cofactor, NADH, and the absent phosphate group, these side chains have been modified in the mutant form.