1u0v: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
New page: left|200px<br /><applet load="1u0v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u0v, resolution 1.90Å" /> '''An Aldol Switch Disc...
 
OCA (talk | contribs)
No edit summary
 
(15 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1u0v.gif|left|200px]]<br /><applet load="1u0v" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1u0v, resolution 1.90&Aring;" />
'''An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization of Specificity of Type III Polyketide Synthases: 18xCHS structure'''<br />


==Overview==
==An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization of Specificity of Type III Polyketide Synthases: 18xCHS structure==
Stilbene synthase (STS) and chalcone synthase (CHS) each catalyze the, formation of a tetraketide intermediate from a CoA-tethered, phenylpropanoid starter and three molecules of malonyl-CoA, but use, different cyclization mechanisms to produce distinct chemical scaffolds, for a variety of plant natural products. Here we present the first STS, crystal structure and identify, by mutagenic conversion of alfalfa CHS, into a functional stilbene synthase, the structural basis for the, evolution of STS cyclization specificity in type III polyketide synthase, (PKS) enzymes. Additional mutagenesis and enzymatic characterization, confirms that electronic effects rather than steric factors balance, competing cyclization specificities in CHS and STS. Finally, we discuss, the problematic in vitro reconstitution of plant stilbenecarboxylate, pathways, using insights from existing biomimetic polyketide cyclization, studies to generate a novel mechanistic hypothesis to explain, stilbenecarboxylate biosynthesis.
<StructureSection load='1u0v' size='340' side='right'caption='[[1u0v]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1u0v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Medicago_sativa Medicago sativa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U0V 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]] 1.9&#8491;</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=1u0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u0v OCA], [https://pdbe.org/1u0v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u0v RCSB], [https://www.ebi.ac.uk/pdbsum/1u0v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u0v ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHS2_MEDSA CHS2_MEDSA] The primary product of this enzyme is 4,2',4',6'-tetrahydroxychalcone (also termed naringenin-chalcone or chalcone) which can under specific conditions spontaneously isomerize into naringenin.<ref>PMID:10653632</ref> <ref>PMID:11732902</ref> <ref>PMID:11959984</ref> <ref>PMID:15380179</ref>
== 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/u0/1u0v_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=1u0v ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Stilbene synthase (STS) and chalcone synthase (CHS) each catalyze the formation of a tetraketide intermediate from a CoA-tethered phenylpropanoid starter and three molecules of malonyl-CoA, but use different cyclization mechanisms to produce distinct chemical scaffolds for a variety of plant natural products. Here we present the first STS crystal structure and identify, by mutagenic conversion of alfalfa CHS into a functional stilbene synthase, the structural basis for the evolution of STS cyclization specificity in type III polyketide synthase (PKS) enzymes. Additional mutagenesis and enzymatic characterization confirms that electronic effects rather than steric factors balance competing cyclization specificities in CHS and STS. Finally, we discuss the problematic in vitro reconstitution of plant stilbenecarboxylate pathways, using insights from existing biomimetic polyketide cyclization studies to generate a novel mechanistic hypothesis to explain stilbenecarboxylate biosynthesis.


==About this Structure==
An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases.,Austin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP Chem Biol. 2004 Sep;11(9):1179-94. PMID:15380179<ref>PMID:15380179</ref>
1U0V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Medicago_sativa Medicago sativa]. Active as [http://en.wikipedia.org/wiki/Naringenin-chalcone_synthase Naringenin-chalcone synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.74 2.3.1.74] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U0V OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases., Austin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP, Chem Biol. 2004 Sep;11(9):1179-94. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15380179 15380179]
</div>
<div class="pdbe-citations 1u0v" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Chalcone synthase|Chalcone synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Medicago sativa]]
[[Category: Medicago sativa]]
[[Category: Naringenin-chalcone synthase]]
[[Category: Austin MB]]
[[Category: Single protein]]
[[Category: Bowman ME]]
[[Category: Austin, M.B.]]
[[Category: Ferrer J-L]]
[[Category: Bowman, M.E.]]
[[Category: Noel JP]]
[[Category: Ferrer, J.L.]]
[[Category: Schroder J]]
[[Category: Noel, J.P.]]
[[Category: Schroder, J.]]
[[Category: aldol switch]]
[[Category: alpha-beta-alpha-beta-alpha fold]]
[[Category: catalytic triad]]
[[Category: condensing enzyme]]
[[Category: engineered resveratrol synthase]]
[[Category: pks]]
[[Category: thiolase fold]]
[[Category: type iii polyketide synthase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:45:31 2007''

Latest revision as of 06:36, 23 August 2023

An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization of Specificity of Type III Polyketide Synthases: 18xCHS structure

1u0v, resolution 1.90Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA