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[[Image:1pe1.gif|left|200px]]


{{Structure
==Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGA==
|PDB= 1pe1 |SIZE=350|CAPTION= <scene name='initialview01'>1pe1</scene>, resolution 1.74&Aring;
<StructureSection load='1pe1' size='340' side='right'caption='[[1pe1]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene> and <scene name='pdbligand=2PG:2-PHOSPHOGLYCERIC ACID'>2PG</scene>
<table><tr><td colspan='2'>[[1pe1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PE1 FirstGlance]. <br>
|ACTIVITY= [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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74&#8491;</td></tr>
|GENE= kdsA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pe1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pe1 OCA], [https://pdbe.org/1pe1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pe1 RCSB], [https://www.ebi.ac.uk/pdbsum/1pe1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pe1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KDSA_AQUAE KDSA_AQUAE]  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pe/1pe1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pe1 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGA'''
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<ref>PMID:14675946</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pe1" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Kdo-8-phosphate synthase|Kdo-8-phosphate synthase]]
 
== References ==
==About this Structure==
<references/>
1PE1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PE1 OCA].
__TOC__
 
</StructureSection>
==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:[http://www.ncbi.nlm.nih.gov/pubmed/14675946 14675946]
[[Category: 3-deoxy-8-phosphooctulonate synthase]]
[[Category: Aquifex aeolicus]]
[[Category: Aquifex aeolicus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Birck, M R.]]
[[Category: Birck MR]]
[[Category: Coutrot, P.]]
[[Category: Coutrot P]]
[[Category: Gatti, D L.]]
[[Category: Gatti DL]]
[[Category: Grison, C.]]
[[Category: Grison C]]
[[Category: Petek, S.]]
[[Category: Petek S]]
[[Category: Wang, J.]]
[[Category: Wang J]]
[[Category: Woodard, R W.]]
[[Category: Woodard RW]]
[[Category: Xu, X.]]
[[Category: Xu X]]
[[Category: 2PG]]
[[Category: CD]]
[[Category: PO4]]
[[Category: beta(8)/alpha(8) barrel]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:23:10 2008''

Latest revision as of 12:41, 16 August 2023

Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGAAquifex aeolicus KDO8PS in complex with cadmium and 2-PGA

Structural highlights

1pe1 is a 2 chain structure with sequence from Aquifex aeolicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.74Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KDSA_AQUAE

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Xu X, Wang J, Grison C, Petek S, Coutrot P, Birck MR, Woodard RW, Gatti DL. Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase. Drug Des Discov. 2003;18(2-3):91-9. PMID:14675946

1pe1, resolution 1.74Å

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