4kct

Pyruvate kinase (PYK) from Trypanosoma brucei soaked with Oxaloacetate

spinqualitylabelsall models 4kct, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kct is a 2 chain structure with sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: FDP, GOL, K, MG, PYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KPYK1_TRYBB Publication Abstract from PubMed The phosphotransfer mechanism of pyruvate kinases (PYKs) has been studied in detail, but the mechanism of the intrinsic decarboxylase reaction catalysed by PYKs is still unknown. 1H NMR was used in this work to follow oxaloacetate (OAA) decarboxylation by trypanosomatid and human PYKs confirming that the decarboxylase activity is conserved across distantly related species. Crystal structures of Trypanosoma brucei PYK (TbPYK) complexed with the product of the decarboxylase reaction (pyruvate), and a series of substrate analogues (D-malate, alpha-ketoglutarate and oxalate) show that the OAA analogues bind to the kinase active site with similar binding modes, confirming that both decarboxylase and kinase activities share a common site for substrate binding and catalysis. Decarboxylation of OAA as monitored by NMR for TbPYK is relatively slow with turn-over values of 0.86 s-1 and 1.47 s-1 in the absence and presence of fructose 2,6-bisphosphate (F26BP), respectively. Human M1PYK has a measured turn-over value of 0.50 s-1. The X-ray structures explain why the decarboxylation activity is specific for OAA and is not general for alpha-keto acid analogues. Conservation of the decarboxylase reaction across divergent species is a consequence of piggybacking on the conserved kinase mechanism which requires a stabilised enol intermediate. Pyruvate kinases have an intrinsic and conserved decarboxylase activity.,Zhong W, Morgan HP, Nowicki MW, McNae IW, Yuan M, Bella J, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD Biochem J. 2013 Dec 13. PMID:24328825 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate kinase 3D structures

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