2q99: Difference between revisions

Revision as of 19:37, 21 February 2008

Crystal Structure of Saccharopine Dehydrogenase from Saccharomyces cerevisiae

OverviewOverview

The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development.

About this StructureAbout this Structure

2Q99 is a Single protein structure of sequence from Saccharomyces cerevisiae. Active as Saccharopine dehydrogenase (NAD(+), L-lysine-forming), with EC number 1.5.1.7 Full crystallographic information is available from OCA.

ReferenceReference

Structural studies of the final enzyme in the alpha-aminoadipate pathway-saccharopine dehydrogenase from Saccharomyces cerevisiae., Burk DL, Hwang J, Kwok E, Marrone L, Goodfellow V, Dmitrienko GI, Berghuis AM, J Mol Biol. 2007 Oct 26;373(3):745-54. Epub 2007 Aug 24. PMID:17854830

Page seeded by OCA on Thu Feb 21 18:37:22 2008

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 ==Overview==
-The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase, (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two, domains with similar dinucleotide binding folds with a deep cleft at the, interface. The structure reveals homology to alanine dehydrogense, despite, low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially, important for substrate binding and/or catalysis, consistent with a proton, shuttle mechanism. Furthermore, the model suggests that a conformational, change is required for catalysis and that residues Lys99 and Asp281 may be, instrumental in mediating this change. Analysis of the crystal structure, in the context of other homologous enzymes from pathogenic fungi and human, sources sheds light into the suitability of SDH as a target for, antimicrobial drug development.
+The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==Reference==
-Structural Studies of the Final Enzyme in the alpha-Aminoadipate Pathway-Saccharopine Dehydrogenase from Saccharomyces cerevisiae., Burk DL, Hwang J, Kwok E, Marrone L, Goodfellow V, Dmitrienko GI, Berghuis AM, J Mol Biol. 2007 Oct 26;373(3):745-54. Epub 2007 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17854830 17854830]
+Structural studies of the final enzyme in the alpha-aminoadipate pathway-saccharopine dehydrogenase from Saccharomyces cerevisiae., Burk DL, Hwang J, Kwok E, Marrone L, Goodfellow V, Dmitrienko GI, Berghuis AM, J Mol Biol. 2007 Oct 26;373(3):745-54. Epub 2007 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17854830 17854830]
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Saccharopine dehydrogenase (NAD(+), L-lysine-forming)]]
 [[Category: Single protein]]
-[[Category: Berghuis, A.M.]]
+[[Category: Berghuis, A M.]]
-[[Category: Burk, D.L.]]
+[[Category: Burk, D L.]]
 [[Category: alpha-aminoadipate pathway]]
 [[Category: alpha/beta protein]]
@@ Line 23: / Line 23: @@
 [[Category: rossmann fold]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:22:43 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:22 2008''