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New page: left|200px<br /><applet load="1yon" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yon, resolution 1.95Å" /> '''Escherichia coli ket...
 
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[[Image:1yon.gif|left|200px]]<br /><applet load="1yon" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1yon, resolution 1.95&Aring;" />
'''Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate'''<br />


==Overview==
==Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate==
The crystal structure of Escherichia coli ketopantoate reductase in, complex with 2'-monophosphoadenosine 5'-diphosphoribose, a fragment of, NADP+ that lacks the nicotinamide ring, is reported. The ligand is bound, at the enzyme active site in the opposite orientation to that observed for, NADP+, with the adenine ring occupying the lipophilic nicotinamide pocket., Isothermal titration calorimetry with R31A and N98A mutants of the enzyme, is used to show that the unusual ;reversed binding mode' observed in the, crystal is triggered by changes in the protonation of binding groups at, low pH. This research has important implications for fragment-based, approaches to drug design, namely that the crystallization conditions and, the chemical modification of ligands can have unexpected effects on the, binding modes.
<StructureSection load='1yon' size='340' side='right'caption='[[1yon]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1yon]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YON 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2R:[(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+[(2R,3S,4R,5R)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>A2R</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=1yon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yon OCA], [https://pdbe.org/1yon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yon RCSB], [https://www.ebi.ac.uk/pdbsum/1yon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yon ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PANE_ECOLI PANE_ECOLI] Catalyzes the NADPH-dependent reduction of ketopantoate into pantoic acid.
== 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/yo/1yon_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=1yon ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of Escherichia coli ketopantoate reductase in complex with 2'-monophosphoadenosine 5'-diphosphoribose, a fragment of NADP+ that lacks the nicotinamide ring, is reported. The ligand is bound at the enzyme active site in the opposite orientation to that observed for NADP+, with the adenine ring occupying the lipophilic nicotinamide pocket. Isothermal titration calorimetry with R31A and N98A mutants of the enzyme is used to show that the unusual ;reversed binding mode' observed in the crystal is triggered by changes in the protonation of binding groups at low pH. This research has important implications for fragment-based approaches to drug design, namely that the crystallization conditions and the chemical modification of ligands can have unexpected effects on the binding modes.


==About this Structure==
pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study.,Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):171-8. Epub 2007, Jan 16. PMID:17242510<ref>PMID:17242510</ref>
1YON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with APX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/2-dehydropantoate_2-reductase 2-dehydropantoate 2-reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.169 1.1.1.169] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YON OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study., Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C, Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):171-8. Epub 2007, Jan 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17242510 17242510]
</div>
[[Category: 2-dehydropantoate 2-reductase]]
<div class="pdbe-citations 1yon" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abell, C.]]
[[Category: Abell C]]
[[Category: Blundell, T.L.]]
[[Category: Blundell TL]]
[[Category: Ciulli, A.]]
[[Category: Ciulli A]]
[[Category: Lobley, C.M.C.]]
[[Category: Lobley CMC]]
[[Category: Smith, A.G.]]
[[Category: Smith AG]]
[[Category: Tuck, K.L.]]
[[Category: Tuck KL]]
[[Category: Williams, G.]]
[[Category: Williams G]]
[[Category: APX]]
[[Category: 2'-monophosphoadenosine-5'-diphosphate]]
[[Category: ketopantoate]]
[[Category: nadp+ dependent]]
[[Category: pantothenate pathway]]
[[Category: secondary alcohol dehydrogenase]]
 
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