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3ils

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Revision as of 04:54, 5 August 2016

The Thioesterase Domain from PksA

Structural highlights

3ils is a 1 chain structure with sequence from Asppa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PksA, pksL1 (ASPPA)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PKSL1_ASPPA] Combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor norsolorinic acid anthrone (noranthrone) in the aflatoxin biosynthesis pathway. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Polyketide natural products possess diverse architectures and biological functions and share a subset of biosynthetic steps with fatty acid synthesis. The final transformation catalyzed by both polyketide synthases (PKSs) and fatty acid synthases is most often carried out by a thioesterase (TE). The synthetic versatility of TE domains in fungal nonreducing, iterative PKSs (NR-PKSs) has been shown to extend to Claisen cyclase (CLC) chemistry by catalyzing C-C ring closure reactions as opposed to thioester hydrolysis or O-C/N-C macrocyclization observed in previously reported TE structures. Catalysis of C-C bond formation as a product release mechanism dramatically expands the synthetic potential of PKSs, but how this activity was acquired has remained a mystery. We report the biochemical and structural analyses of the TE/CLC domain in polyketide synthase A, the multidomain PKS central to the biosynthesis of aflatoxin B(1), a potent environmental carcinogen. Mutagenesis experiments confirm the predicted identity of the catalytic triad and its role in catalyzing the final Claisen-type cyclization to the aflatoxin precursor, norsolorinic acid anthrone. The 1.7 A crystal structure displays an alpha/beta-hydrolase fold in the catalytic closed form with a distinct hydrophobic substrate-binding chamber. We propose that a key rotation of the substrate side chain coupled to a protein conformational change from the open to closed form spatially governs substrate positioning and C-C cyclization. The biochemical studies, the 1.7 A crystal structure of the TE/CLC domain, and intermediate modeling afford the first mechanistic insights into this widely distributed C-C bond-forming class of TEs.

Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis.,Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC Proc Natl Acad Sci U S A. 2010 Mar 23. PMID:20332208^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yu J, Chang PK, Ehrlich KC, Cary JW, Bhatnagar D, Cleveland TE, Payne GA, Linz JE, Woloshuk CP, Bennett JW. Clustered pathway genes in aflatoxin biosynthesis. Appl Environ Microbiol. 2004 Mar;70(3):1253-62. PMID:15006741
↑ Crawford JM, Thomas PM, Scheerer JR, Vagstad AL, Kelleher NL, Townsend CA. Deconstruction of iterative multidomain polyketide synthase function. Science. 2008 Apr 11;320(5873):243-6. doi: 10.1126/science.1154711. PMID:18403714 doi:http://dx.doi.org/10.1126/science.1154711
↑ Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC. Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis. Proc Natl Acad Sci U S A. 2010 Mar 23. PMID:20332208

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ils"

@@ Line 1: / Line 1: @@
 ==The Thioesterase Domain from PksA==
 <StructureSection load='3ils' size='340' side='right' caption='[[3ils]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ils]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_parasiticus Aspergillus parasiticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ILS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ILS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ils]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Asppa Asppa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ILS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ILS FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 Aspergillus parasiticus])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PksA, pksL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5067 ASPPA])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ils FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ils OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ils RCSB], [http://www.ebi.ac.uk/pdbsum/3ils PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ils FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ils OCA], [http://pdbe.org/3ils PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ils RCSB], [http://www.ebi.ac.uk/pdbsum/3ils PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ils ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3ils ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ils" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Aspergillus parasiticus]]
+[[Category: Asppa]]
 [[Category: Korman, T P]]
 [[Category: A/b hydrolase]]

3ils

From Proteopedia

Revision as of 04:54, 5 August 2016

The Thioesterase Domain from PksA

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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