2ez8
From Proteopedia
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[[Image:2ez8.gif|left|200px]] | [[Image:2ez8.gif|left|200px]] | ||
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'''Pyruvate oxidase variant F479W in complex with reaction intermediate 2-lactyl-thiamin diphosphate''' | '''Pyruvate oxidase variant F479W in complex with reaction intermediate 2-lactyl-thiamin diphosphate''' | ||
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[[Category: Tittmann, K.]] | [[Category: Tittmann, K.]] | ||
[[Category: Wille, G.]] | [[Category: Wille, G.]] | ||
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- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:16:41 2008'' | |
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Revision as of 00:16, 4 May 2008
Pyruvate oxidase variant F479W in complex with reaction intermediate 2-lactyl-thiamin diphosphate
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.
About this Structure
2EZ8 is a Single protein structure of sequence from Lactobacillus plantarum. Full crystallographic information is available from OCA.
Reference
The catalytic cycle of a thiamin diphosphate enzyme examined by cryocrystallography., Wille G, Meyer D, Steinmetz A, Hinze E, Golbik R, Tittmann K, Nat Chem Biol. 2006 Jun;2(6):324-8. Epub 2006 May 7. PMID:16680160 Page seeded by OCA on Sun May 4 03:16:41 2008