1ixn
From Proteopedia
(New page: 200px<br /><applet load="1ixn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ixn, resolution 2.3Å" /> '''Enzyme-Substrate Comp...) |
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| - | [[Image:1ixn.gif|left|200px]]<br /><applet load="1ixn" size=" | + | [[Image:1ixn.gif|left|200px]]<br /><applet load="1ixn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ixn, resolution 2.3Å" /> | caption="1ixn, resolution 2.3Å" /> | ||
'''Enzyme-Substrate Complex of Pyridoxine 5'-Phosphate Synthase'''<br /> | '''Enzyme-Substrate Complex of Pyridoxine 5'-Phosphate Synthase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pyridoxine 5'-phosphate (PNP) synthase is the last enzyme in the de novo | + | 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== | ==About this Structure== | ||
| - | 1IXN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with DXP and G3P as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1IXN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=DXP:'>DXP</scene> and <scene name='pdbligand=G3P:'>G3P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IXN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:16:44 2008'' |
Revision as of 11:16, 21 February 2008
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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 and 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
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