1pck

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1pck" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pck, resolution 1.80&Aring;" /> '''Aquifex aeolicus KDO...)
Current revision (09:41, 16 August 2023) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1pck.jpg|left|200px]]<br /><applet load="1pck" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1pck, resolution 1.80&Aring;" />
 
-
'''Aquifex aeolicus KDO8PS in complex with Z-methyl-PEP'''<br />
 
-
==Overview==
+
==Aquifex aeolicus KDO8PS in complex with Z-methyl-PEP==
-
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.
+
<StructureSection load='1pck' size='340' side='right'caption='[[1pck]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1pck]] 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=1PCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PCK 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]] 1.8&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=PEZ:2-(PHOSPHONOOXY)BUTANOIC+ACID'>PEZ</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=1pck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pck OCA], [https://pdbe.org/1pck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pck RCSB], [https://www.ebi.ac.uk/pdbsum/1pck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pck 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/pc/1pck_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=1pck 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.
-
==About this Structure==
+
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>
-
1PCK 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 PO4, CD and PEZ 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PCK OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=14675946 14675946]
+
</div>
-
[[Category: 3-deoxy-8-phosphooctulonate synthase]]
+
<div class="pdbe-citations 1pck" style="background-color:#fffaf0;"></div>
-
[[Category: Aquifex aeolicus]]
+
-
[[Category: Single protein]]
+
-
[[Category: Birck, M.]]
+
-
[[Category: Coutrot, P.]]
+
-
[[Category: Gatti, D.L.]]
+
-
[[Category: Grison, C.]]
+
-
[[Category: Petek, S.]]
+
-
[[Category: Wang, J.]]
+
-
[[Category: Woodard, R.W.]]
+
-
[[Category: Xu, X.]]
+
-
[[Category: CD]]
+
-
[[Category: PEZ]]
+
-
[[Category: PO4]]
+
-
[[Category: beta(8)/alpha(8) barrel]]
+
-
[[Category: lyase]]
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:41:17 2007''
+
==See Also==
 +
*[[Kdo-8-phosphate synthase|Kdo-8-phosphate synthase]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Aquifex aeolicus]]
 +
[[Category: Large Structures]]
 +
[[Category: Birck M]]
 +
[[Category: Coutrot P]]
 +
[[Category: Gatti DL]]
 +
[[Category: Grison C]]
 +
[[Category: Petek S]]
 +
[[Category: Wang J]]
 +
[[Category: Woodard RW]]
 +
[[Category: Xu X]]

Current revision

Aquifex aeolicus KDO8PS in complex with Z-methyl-PEP

PDB ID 1pck

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pck"
Personal tools