1chu: Difference between revisions

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[[Image:1chu.gif|left|200px]]<br /><applet load="1chu" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1chu.gif|left|200px]]<br /><applet load="1chu" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1chu, resolution 2.2Å" />

'''STRUCTURE OF L-ASPARTATE OXIDASE: IMPLICATIONS FOR THE SUCCINATE DEHYDROGENASE/ FUMARATE REDUCATSE FAMILY'''<br />

==Overview==

BACKGROUND: Given the vital role of NAD+ in cell metabolism, the enzymes, involved in bacterial de novo NAD+ biosynthesis are possible targets for, drug design against pathogenic bacteria. The first reaction in the pathway, is catalysed by L-aspartate oxidase (LASPO), a flavoenzyme that converts, aspartate to iminoaspartate using either molecular oxygen or fumarate as, electron acceptors. LASPO has considerable sequence homology with the, flavoprotein subunits of succinate dehydrogenase (SDH) and fumarate, reductase (FRD). RESULTS: The crystal structure of the apoform of LASPO, from Escherichia coli has been determined to 2.2 A resolution. The enzyme, shows a novel fold for an FAD-dependent protein, comprising a three-domain, structure: an FAD-binding domain with the dinucleotide-binding fold, a, C-terminal three-helical bundle domain, and an alpha + beta capping, domain, which is topologically similar to the small subunit of spinach, ribulose-1,5-bisphosphate carboxylase/oxygenase. The interface between the, FAD-binding and capping domains defines a cleft in which the active site, is located. CONCLUSIONS: A number of strictly conserved residues present, in all three domains indicate that LASPO, SDH and FRD share the same, overall folding topology. Many of these conserved residues are in the, FAD-binding site and active centre, suggesting a similar catalytic, mechanism. Thus, LASPO, SDH and FRD form a class of functionally and, structurally related oxidoreductases that are all able to reduce fumarate, and to oxidise a dicarboxylate substrate.

BACKGROUND: Given the vital role of NAD+ in cell metabolism, the enzymes involved in bacterial de novo NAD+ biosynthesis are possible targets for drug design against pathogenic bacteria. The first reaction in the pathway is catalysed by L-aspartate oxidase (LASPO), a flavoenzyme that converts aspartate to iminoaspartate using either molecular oxygen or fumarate as electron acceptors. LASPO has considerable sequence homology with the flavoprotein subunits of succinate dehydrogenase (SDH) and fumarate reductase (FRD). RESULTS: The crystal structure of the apoform of LASPO from Escherichia coli has been determined to 2.2 A resolution. The enzyme shows a novel fold for an FAD-dependent protein, comprising a three-domain structure: an FAD-binding domain with the dinucleotide-binding fold, a C-terminal three-helical bundle domain, and an alpha + beta capping domain, which is topologically similar to the small subunit of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase. The interface between the FAD-binding and capping domains defines a cleft in which the active site is located. CONCLUSIONS: A number of strictly conserved residues present in all three domains indicate that LASPO, SDH and FRD share the same overall folding topology. Many of these conserved residues are in the FAD-binding site and active centre, suggesting a similar catalytic mechanism. Thus, LASPO, SDH and FRD form a class of functionally and structurally related oxidoreductases that are all able to reduce fumarate and to oxidise a dicarboxylate substrate.

==About this Structure==

1CHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1CHU OCA].

1CHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CHU OCA].

==Reference==

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[[Category: oxidoreductase]]

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@@ Line 1: / Line 1: @@
-[[Image:1chu.gif|left|200px]]<br /><applet load="1chu" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1chu.gif|left|200px]]<br /><applet load="1chu" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1chu, resolution 2.2&Aring;" />
 '''STRUCTURE OF L-ASPARTATE OXIDASE: IMPLICATIONS FOR THE SUCCINATE DEHYDROGENASE/ FUMARATE REDUCATSE FAMILY'''<br />
 ==Overview==
-BACKGROUND: Given the vital role of NAD+ in cell metabolism, the enzymes, involved in bacterial de novo NAD+ biosynthesis are possible targets for, drug design against pathogenic bacteria. The first reaction in the pathway, is catalysed by L-aspartate oxidase (LASPO), a flavoenzyme that converts, aspartate to iminoaspartate using either molecular oxygen or fumarate as, electron acceptors. LASPO has considerable sequence homology with the, flavoprotein subunits of succinate dehydrogenase (SDH) and fumarate, reductase (FRD). RESULTS: The crystal structure of the apoform of LASPO, from Escherichia coli has been determined to 2.2 A resolution. The enzyme, shows a novel fold for an FAD-dependent protein, comprising a three-domain, structure: an FAD-binding domain with the dinucleotide-binding fold, a, C-terminal three-helical bundle domain, and an alpha + beta capping, domain, which is topologically similar to the small subunit of spinach, ribulose-1,5-bisphosphate carboxylase/oxygenase. The interface between the, FAD-binding and capping domains defines a cleft in which the active site, is located. CONCLUSIONS: A number of strictly conserved residues present, in all three domains indicate that LASPO, SDH and FRD share the same, overall folding topology. Many of these conserved residues are in the, FAD-binding site and active centre, suggesting a similar catalytic, mechanism. Thus, LASPO, SDH and FRD form a class of functionally and, structurally related oxidoreductases that are all able to reduce fumarate, and to oxidise a dicarboxylate substrate.
+BACKGROUND: Given the vital role of NAD+ in cell metabolism, the enzymes involved in bacterial de novo NAD+ biosynthesis are possible targets for drug design against pathogenic bacteria. The first reaction in the pathway is catalysed by L-aspartate oxidase (LASPO), a flavoenzyme that converts aspartate to iminoaspartate using either molecular oxygen or fumarate as electron acceptors. LASPO has considerable sequence homology with the flavoprotein subunits of succinate dehydrogenase (SDH) and fumarate reductase (FRD). RESULTS: The crystal structure of the apoform of LASPO from Escherichia coli has been determined to 2.2 A resolution. The enzyme shows a novel fold for an FAD-dependent protein, comprising a three-domain structure: an FAD-binding domain with the dinucleotide-binding fold, a C-terminal three-helical bundle domain, and an alpha + beta capping domain, which is topologically similar to the small subunit of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase. The interface between the FAD-binding and capping domains defines a cleft in which the active site is located. CONCLUSIONS: A number of strictly conserved residues present in all three domains indicate that LASPO, SDH and FRD share the same overall folding topology. Many of these conserved residues are in the FAD-binding site and active centre, suggesting a similar catalytic mechanism. Thus, LASPO, SDH and FRD form a class of functionally and structurally related oxidoreductases that are all able to reduce fumarate and to oxidise a dicarboxylate substrate.
 ==About this Structure==
-CHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CHU OCA].
+CHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CHU OCA].
 ==Reference==
@@ Line 19: / Line 19: @@
 [[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:28:13 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:06:12 2008''