1pe1: Difference between revisions

Revision as of 04:58, 3 May 2008

Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGA

OverviewOverview

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 StructureAbout this Structure

1PE1 is a Single protein structure of sequence from Aquifex aeolicus. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sat May 3 04:58:59 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1pe1.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1pe1", creates the "Structure Box" on the page.
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+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=2PG:2-PHOSPHOGLYCERIC+ACID'>2PG</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
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-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= kdsA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus])
+-->
-|DOMAIN=
+{{STRUCTURE_1pe1|  PDB=1pe1  |  SCENE=  }}
-|RELATEDENTRY=[[1fws|1FWS]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pe1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pe1 OCA], [http://www.ebi.ac.uk/pdbsum/1pe1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pe1 RCSB]</span>
-}}
 '''Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGA'''
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 [[Category: Woodard, R W.]]
 [[Category: Xu, X.]]
-[[Category: beta(8)/alpha(8) barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 04:58:59 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:58:25 2008''