2ez4: Difference between revisions

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[[Image:2ez4.gif|left|200px]]<br /><applet load="2ez4" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2ez4.gif|left|200px]]<br /><applet load="2ez4" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2ez4, resolution 2.03Å" />

'''Pyruvate oxidase variant F479W'''<br />

==Overview==

Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the, biologically active form of vitamin B(1), are involved in numerous, metabolic pathways in all organisms. Although a theory of the cofactor's, underlying reaction mechanism has been established over the last five, decades, the three-dimensional structures of most major reaction, intermediates of ThDP enzymes have remained elusive. Here, we report the, X-ray structures of key intermediates in the oxidative decarboxylation of, pyruvate, a central reaction in carbon metabolism catalyzed by the ThDP-, and flavin-dependent enzyme pyruvate oxidase (POX)3 from Lactobacillus, plantarum. The structures of 2-lactyl-ThDP (LThDP, 2) and its stable, phosphonate analog, of 2-hydroxyethyl-ThDP (HEThDP, 3) enamine and of, 2-acetyl-ThDP (AcThDP, 4; all shown bound to the enzyme's active site), provide profound insights into the chemical mechanisms and the, stereochemical course of thiamin catalysis. These snapshots also suggest a, mechanism for a phosphate-linked acyl transfer coupled to electron, transfer in a radical reaction of pyruvate oxidase.

Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the biologically active form of vitamin B(1), are involved in numerous metabolic pathways in all organisms. Although a theory of the cofactor's underlying reaction mechanism has been established over the last five decades, the three-dimensional structures of most major reaction intermediates of ThDP enzymes have remained elusive. Here, we report the X-ray structures of key intermediates in the oxidative decarboxylation of pyruvate, a central reaction in carbon metabolism catalyzed by the ThDP- and flavin-dependent enzyme pyruvate oxidase (POX)3 from Lactobacillus plantarum. The structures of 2-lactyl-ThDP (LThDP, 2) and its stable phosphonate analog, of 2-hydroxyethyl-ThDP (HEThDP, 3) enamine and of 2-acetyl-ThDP (AcThDP, 4; all shown bound to the enzyme's active site) provide profound insights into the chemical mechanisms and the stereochemical course of thiamin catalysis. These snapshots also suggest a mechanism for a phosphate-linked acyl transfer coupled to electron transfer in a radical reaction of pyruvate oxidase.

==About this Structure==

2EZ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_plantarum Lactobacillus plantarum] with MG, NA, PO4, TPP and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_oxidase Pyruvate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.3.3 1.2.3.3] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2EZ4 OCA].

2EZ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_plantarum Lactobacillus plantarum] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=TPP:'>TPP</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_oxidase Pyruvate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.3.3 1.2.3.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EZ4 OCA].

==Reference==

Line 27:

[[Category: tpp enzyme]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 10:14:~~32 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:15:59 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2ez4.gif|left|200px]]<br /><applet load="2ez4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2ez4.gif|left|200px]]<br /><applet load="2ez4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2ez4, resolution 2.03&Aring;" />
 '''Pyruvate oxidase variant F479W'''<br />
 ==Overview==
-Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the, biologically active form of vitamin B(1), are involved in numerous, metabolic pathways in all organisms. Although a theory of the cofactor's, underlying reaction mechanism has been established over the last five, decades, the three-dimensional structures of most major reaction, intermediates of ThDP enzymes have remained elusive. Here, we report the, X-ray structures of key intermediates in the oxidative decarboxylation of, pyruvate, a central reaction in carbon metabolism catalyzed by the ThDP-, and flavin-dependent enzyme pyruvate oxidase (POX)3 from Lactobacillus, plantarum. The structures of 2-lactyl-ThDP (LThDP, 2) and its stable, phosphonate analog, of 2-hydroxyethyl-ThDP (HEThDP, 3) enamine and of, 2-acetyl-ThDP (AcThDP, 4; all shown bound to the enzyme's active site), provide profound insights into the chemical mechanisms and the, stereochemical course of thiamin catalysis. These snapshots also suggest a, mechanism for a phosphate-linked acyl transfer coupled to electron, transfer in a radical reaction of pyruvate oxidase.
+Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the biologically active form of vitamin B(1), are involved in numerous metabolic pathways in all organisms. Although a theory of the cofactor's underlying reaction mechanism has been established over the last five decades, the three-dimensional structures of most major reaction intermediates of ThDP enzymes have remained elusive. Here, we report the X-ray structures of key intermediates in the oxidative decarboxylation of pyruvate, a central reaction in carbon metabolism catalyzed by the ThDP- and flavin-dependent enzyme pyruvate oxidase (POX)3 from Lactobacillus plantarum. The structures of 2-lactyl-ThDP (LThDP, 2) and its stable phosphonate analog, of 2-hydroxyethyl-ThDP (HEThDP, 3) enamine and of 2-acetyl-ThDP (AcThDP, 4; all shown bound to the enzyme's active site) provide profound insights into the chemical mechanisms and the stereochemical course of thiamin catalysis. These snapshots also suggest a mechanism for a phosphate-linked acyl transfer coupled to electron transfer in a radical reaction of pyruvate oxidase.
 ==About this Structure==
-EZ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_plantarum Lactobacillus plantarum] with MG, NA, PO4, TPP and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_oxidase Pyruvate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.3.3 1.2.3.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2EZ4 OCA].
+EZ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_plantarum Lactobacillus plantarum] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=TPP:'>TPP</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_oxidase Pyruvate oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.3.3 1.2.3.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EZ4 OCA].
 ==Reference==
@@ Line 27: / Line 27: @@
 [[Category: tpp enzyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:14:32 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:15:59 2008''