1ixn
From Proteopedia
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Enzyme-Substrate Complex of Pyridoxine 5'-Phosphate Synthase
Overview
Pyridoxine 5'-phosphate (PNP) synthase is the last enzyme in the de novo, biosynthesis of vitamin B(6) catalyzing the complicated ring-closure, reaction between 1-deoxy-D-xylulose-5-phosphate and, 1-amino-acetone-3-phosphate. Here we present the crystal structures of, four PNP synthase complexes with substrates and substrate analogs. While, the overall fold of the enzyme is conserved in all complexes, characteristic readjustments were observed in the active site. The, complementary structural information allowed us to postulate a detailed, reaction mechanism. The observed binding mode of substrates indicates how, the first reaction intermediate, the Schiff-base conjugate, is formed. The, most important mechanistic features are the presence of two, phosphate-binding sites with distinct affinities and the existence of a, water relay system for the release of reaction water molecules., Furthermore, the complexes provide the basis to rationalize the, open-closed transition of a flexible loop located on the C-terminal side, of the TIM-barrel. Binding of both substrate molecules to the active site, seems to be a prerequisite to trigger this transition. Highly conserved, mechanistically important residues in the PNP synthase family imply a, similar active site organization and reaction mechanism for all family, members. Due to the exclusive presence of PNP synthase in a subset of, eubacteria, including several well-known pathogens, and due to its, outstanding physiological importance for these organisms, the enzyme, appears to be a promising novel target for antibacterial drug design.
About this Structure
1IXN is a Single protein structure of sequence from Escherichia coli with DXP and G3P as ligands. Full crystallographic information is available from OCA.
Reference
Enzyme-ligand complexes of pyridoxine 5'-phosphate synthase: implications for substrate binding and catalysis., Garrido-Franco M, Laber B, Huber R, Clausen T, J Mol Biol. 2002 Aug 23;321(4):601-12. PMID:12206776
Page seeded by OCA on Tue Nov 20 17:45:13 2007
