2ez8
From Proteopedia
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| , resolution 1.963Å | |||||||
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| Ligands: | , , , , | ||||||
| Gene: | pox5 (Lactobacillus plantarum) | ||||||
| Activity: | Pyruvate oxidase, with EC number 1.2.3.3 | ||||||
| Related: | 1POW, 1POX, 1Y9D
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 02:55:42 2008
