1u0w
From Proteopedia
(New page: 200px<br /><applet load="1u0w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u0w, resolution 2.00Å" /> '''An Aldol Switch Disc...) |
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| - | [[Image:1u0w.gif|left|200px]]<br /><applet load="1u0w" size=" | + | [[Image:1u0w.gif|left|200px]]<br /><applet load="1u0w" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1u0w, resolution 2.00Å" /> | caption="1u0w, resolution 2.00Å" /> | ||
'''An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization Specificity of Type III Polyketide Synthases: 18xCHS+resveratrol Structure'''<br /> | '''An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization Specificity of Type III Polyketide Synthases: 18xCHS+resveratrol Structure'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Stilbene synthase (STS) and chalcone synthase (CHS) each catalyze the | + | 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== | ==About this Structure== | ||
| - | 1U0W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Medicago_sativa Medicago sativa] with STL as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1U0W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Medicago_sativa Medicago sativa] with <scene name='pdbligand=STL:'>STL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Naringenin-chalcone synthase]] | [[Category: Naringenin-chalcone synthase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Austin, M | + | [[Category: Austin, M B.]] |
| - | [[Category: Bowman, M | + | [[Category: Bowman, M E.]] |
| - | [[Category: Ferrer, J | + | [[Category: Ferrer, J L.]] |
| - | [[Category: Noel, J | + | [[Category: Noel, J P.]] |
[[Category: Schroder, J.]] | [[Category: Schroder, J.]] | ||
[[Category: STL]] | [[Category: STL]] | ||
| Line 34: | Line 34: | ||
[[Category: type iii polyketide synthase]] | [[Category: type iii polyketide synthase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:26 2008'' |
Revision as of 13:19, 21 February 2008
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An Aldol Switch Discovered in Stilbene Synthases Mediates Cyclization Specificity of Type III Polyketide Synthases: 18xCHS+resveratrol Structure
Overview
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
1U0W is a Single protein structure of sequence from Medicago sativa with as ligand. Active as Naringenin-chalcone synthase, with EC number 2.3.1.74 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 15:19:26 2008
Categories: Medicago sativa | Naringenin-chalcone synthase | Single protein | Austin, M B. | Bowman, M E. | Ferrer, J L. | Noel, J P. | Schroder, J. | STL | Aldol switch | Alpha-beta-alpha-beta-alpha fold | Catalytic triad | Chalcone synthase | Chs | Condensing enzyme | Engineered resveratrol synthase | Pks | Rs | Stilbene synthase | Sts | Thiolase fold | Type iii polyketide synthase
