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==Aquifex aeolicus KDO8PS in complex with cadmium and 2-PGA== | |||
<StructureSection load='1pe1' size='340' side='right'caption='[[1pe1]], [[Resolution|resolution]] 1.74Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74Å</td></tr> | |||
<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. | |||
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> | |||
3- | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1pe1" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Kdo-8-phosphate synthase|Kdo-8-phosphate synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Birck | [[Category: Birck MR]] | ||
[[Category: Coutrot | [[Category: Coutrot P]] | ||
[[Category: Gatti | [[Category: Gatti DL]] | ||
[[Category: Grison | [[Category: Grison C]] | ||
[[Category: Petek | [[Category: Petek S]] | ||
[[Category: Wang | [[Category: Wang J]] | ||
[[Category: Woodard | [[Category: Woodard RW]] | ||
[[Category: Xu | [[Category: Xu X]] | ||
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
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed3-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 AlsoReferences |
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