1ixq: Difference between revisions
New page: left|200px<br /><applet load="1ixq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ixq, resolution 2.3Å" /> '''Enzyme-Phosphate2 Com... |
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[[Image:1ixq.gif|left|200px]]<br /><applet load="1ixq" size=" | [[Image:1ixq.gif|left|200px]]<br /><applet load="1ixq" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1ixq, resolution 2.3Å" /> | caption="1ixq, resolution 2.3Å" /> | ||
'''Enzyme-Phosphate2 Complex of Pyridoxine 5'-Phosphate synthase'''<br /> | '''Enzyme-Phosphate2 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== | ||
1IXQ 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 PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1IXQ 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=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IXQ 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 13:16:46 2008'' | ||
Revision as of 14:16, 21 February 2008
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Enzyme-Phosphate2 Complex of Pyridoxine 5'-Phosphate synthase
OverviewOverview
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 StructureAbout this Structure
1IXQ is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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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