2ez9

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spinqualitylabelsall models 2ez9, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Pyruvate oxidase variant F479W in complex with reaction intermediate analogue 2-phosphonolactyl-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

2EZ9 is a Single protein structure of sequence from Lactobacillus plantarum with MG, NA, TDK and FAD as ligands. Active as Pyruvate oxidase, with EC number 1.2.3.3 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

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