1pcw
From Proteopedia
(New page: 200px<br /><applet load="1pcw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pcw, resolution 1.85Å" /> '''Aquifex aeolicus KDO...) |
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| - | [[Image:1pcw.jpg|left|200px]]<br /><applet load="1pcw" size=" | + | [[Image:1pcw.jpg|left|200px]]<br /><applet load="1pcw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pcw, resolution 1.85Å" /> | caption="1pcw, resolution 1.85Å" /> | ||
'''Aquifex aeolicus KDO8PS in complex with cadmium and APP, a bisubstrate inhibitor'''<br /> | '''Aquifex aeolicus KDO8PS in complex with cadmium and APP, a bisubstrate inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated | + | 3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated precursor of KDO, an essential sugar of the lipopolysaccharide of Gram negative bacteria. KDO8P is produced by a specific synthase (KDO8PS) by condensing arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP), with release of inorganic phosphate. As KDO8PS is present in bacteria and plants, but not in mammalian cells, and mutations that inactivate KDO8PS also block cell replication, KDO8PS is a promising target for the design of new antimicrobials that act by blocking lipopolysaccharide biosynthesis. Previous studies have shown that a compound mimicking an intermediate of the condensation reaction is a good ligand and a powerful inhibitor. Here we report on the crystallographic investigation of the binding to KDO8PS of new derivatives of this original inhibitor. The structures of the enzyme in complex with these compounds, and also with the PEP analogs, 2-phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to future strategies for the design of novel inhibitors of KDO8PS. |
==About this Structure== | ==About this Structure== | ||
| - | 1PCW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with CD and H4P as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-deoxy-8-phosphooctulonate_synthase 3-deoxy-8-phosphooctulonate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.55 2.5.1.55] Full crystallographic information is available from [http:// | + | 1PCW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with <scene name='pdbligand=CD:'>CD</scene> and <scene name='pdbligand=H4P:'>H4P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-deoxy-8-phosphooctulonate_synthase 3-deoxy-8-phosphooctulonate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.55 2.5.1.55] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PCW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Birck, M.]] | [[Category: Birck, M.]] | ||
[[Category: Coutrot, P.]] | [[Category: Coutrot, P.]] | ||
| - | [[Category: Gatti, D | + | [[Category: Gatti, D L.]] |
[[Category: Grison, C.]] | [[Category: Grison, C.]] | ||
[[Category: Petek, S.]] | [[Category: Petek, S.]] | ||
[[Category: Wang, J.]] | [[Category: Wang, J.]] | ||
| - | [[Category: Woodard, R | + | [[Category: Woodard, R W.]] |
[[Category: Xu, X.]] | [[Category: Xu, X.]] | ||
[[Category: CD]] | [[Category: CD]] | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:27:34 2008'' |
Revision as of 12:27, 21 February 2008
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Aquifex aeolicus KDO8PS in complex with cadmium and APP, a bisubstrate inhibitor
Overview
3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated precursor of KDO, an essential sugar of the lipopolysaccharide of Gram negative bacteria. KDO8P is produced by a specific synthase (KDO8PS) by condensing arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP), with release of inorganic phosphate. As KDO8PS is present in bacteria and plants, but not in mammalian cells, and mutations that inactivate KDO8PS also block cell replication, KDO8PS is a promising target for the design of new antimicrobials that act by blocking lipopolysaccharide biosynthesis. Previous studies have shown that a compound mimicking an intermediate of the condensation reaction is a good ligand and a powerful inhibitor. Here we report on the crystallographic investigation of the binding to KDO8PS of new derivatives of this original inhibitor. The structures of the enzyme in complex with these compounds, and also with the PEP analogs, 2-phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to future strategies for the design of novel inhibitors of KDO8PS.
About this Structure
1PCW is a Single protein structure of sequence from Aquifex aeolicus with and as ligands. Active as 3-deoxy-8-phosphooctulonate synthase, with EC number 2.5.1.55 Full crystallographic information is available from OCA.
Reference
Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase., Xu X, Wang J, Grison C, Petek S, Coutrot P, Birck MR, Woodard RW, Gatti DL, Drug Des Discov. 2003;18(2-3):91-9. PMID:14675946
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