9vex: Difference between revisions

Latest revision as of 05:08, 27 May 2026

Crystal structure of CpaO in complex with beta-CPA

Structural highlights

9vex is a 1 chain structure with sequence from Aspergillus oryzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.66Å
Ligands:	A1MAH, FAD, NDG, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CPAO_ASPOZ Beta-cyclopiazonate dehydrogenase; part of the gene cluster that mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic indole tetramic acid scaffold (PubMed:21608094). The hybrid two module polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cpaS incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal redox-incompetent reductase domain to make and release the tryptophan tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first intermediate in the pathway. CpaS catalyzes a Dieckmann-type cyclization on the N-acetoacetyl-Trp intermediate bound in thioester linkage to the phosphopantetheinyl arm of the T domain to form and release c-AATrp (PubMed:19663400). CpaD then regiospecifically dimethylallylates c-AATrp to form beta-cyclopiazonic acid. CpaD discriminates against free Trp but accepts tryptophan-containing thiohydantoins, diketopiperazines, and linear peptides as substrates for C4-prenylation and also acts as regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived tetramic acid (PubMed:19877600, PubMed:21608094). The beta-cyclopiazonate dehydrogenase cpaO then carries out the dehydrogenation of beta-CPA to yield an unstable enimine product, which is captured by intramolecular cyclization to create the pentacyclic fused scaffold of alpha-cyclopiazonate (PubMed:21608094). Finally, the cytochrome P450 monooxygenase cpaH mediates the conversion of CPA into the less toxic 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza (PubMed:21608094).^[1] ^[2] ^[3]

References

↑ Liu X, Walsh CT. Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan. Biochemistry. 2009 Sep 15;48(36):8746-57. PMID:19663400 doi:10.1021/bi901123r
↑ Liu X, Walsh CT. Characterization of cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate promiscuity and site directed mutagenesis studies. Biochemistry. 2009 Nov 24;48(46):11032-44. PMID:19877600 doi:10.1021/bi901597j
↑ Kato N, Tokuoka M, Shinohara Y, Kawatani M, Uramoto M, Seshime Y, Fujii I, Kitamoto K, Takahashi T, Takahashi S, Koyama Y, Osada H. Genetic safeguard against mycotoxin cyclopiazonic acid production in Aspergillus oryzae. Chembiochem. 2011 Jun 14;12(9):1376-82. PMID:21608094 doi:10.1002/cbic.201000672

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Liu X, Walsh CT. Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan. Biochemistry. 2009 Sep 15;48(36):8746-57. PMID:19663400 doi:10.1021/bi901123r

[2] Liu X, Walsh CT. Characterization of cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate promiscuity and site directed mutagenesis studies. Biochemistry. 2009 Nov 24;48(46):11032-44. PMID:19877600 doi:10.1021/bi901597j

[3] Kato N, Tokuoka M, Shinohara Y, Kawatani M, Uramoto M, Seshime Y, Fujii I, Kitamoto K, Takahashi T, Takahashi S, Koyama Y, Osada H. Genetic safeguard against mycotoxin cyclopiazonic acid production in Aspergillus oryzae. Chembiochem. 2011 Jun 14;12(9):1376-82. PMID:21608094 doi:10.1002/cbic.201000672

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9vex is ON HOLD  until Paper Publication
+==Crystal structure of CpaO in complex with beta-CPA==
+<StructureSection load='9vex' size='340' side='right'caption='[[9vex]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
-Authors: Chang, C.Y., Cheng, T., Kuo, Y.M., Hsiao, P.Y., Wang, M., Wang, N.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9vex]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_oryzae Aspergillus oryzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VEX FirstGlance]. <br>
-Description: Crystal structure of CpaO in complex with beta-CPA
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.66&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1MAH:(3~{Z},5~{S})-5-[[4-(3-methylbut-2-enyl)-1~{H}-indol-3-yl]methyl]-3-(1-oxidanylethylidene)pyrrolidine-2,4-dione'>A1MAH</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-[[Category: Hsiao, P.Y]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9vex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vex OCA], [https://pdbe.org/9vex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vex RCSB], [https://www.ebi.ac.uk/pdbsum/9vex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vex ProSAT]</span></td></tr>
-[[Category: Wang, M]]
+</table>
-[[Category: Chang, C.Y]]
+== Function ==
-[[Category: Wang, N]]
+[https://www.uniprot.org/uniprot/CPAO_ASPOZ CPAO_ASPOZ] Beta-cyclopiazonate dehydrogenase; part of the gene cluster that mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic indole tetramic acid scaffold (PubMed:21608094). The hybrid two module polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cpaS incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal redox-incompetent reductase domain to make and release the tryptophan tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first intermediate in the pathway. CpaS catalyzes a Dieckmann-type cyclization on the N-acetoacetyl-Trp intermediate bound in thioester linkage to the phosphopantetheinyl arm of the T domain to form and release c-AATrp (PubMed:19663400). CpaD then regiospecifically dimethylallylates c-AATrp to form beta-cyclopiazonic acid. CpaD discriminates against free Trp but accepts tryptophan-containing thiohydantoins, diketopiperazines, and linear peptides as substrates for C4-prenylation and also acts as regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived tetramic acid (PubMed:19877600, PubMed:21608094). The beta-cyclopiazonate dehydrogenase cpaO then carries out the dehydrogenation of beta-CPA to yield an unstable enimine product, which is captured by intramolecular cyclization to create the pentacyclic fused scaffold of alpha-cyclopiazonate (PubMed:21608094). Finally, the cytochrome P450 monooxygenase cpaH mediates the conversion of CPA into the less toxic 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza (PubMed:21608094).<ref>PMID:19663400</ref> <ref>PMID:19877600</ref> <ref>PMID:21608094</ref>
-[[Category: Kuo, Y.M]]
+== References ==
-[[Category: Cheng, T]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Aspergillus oryzae]]
+[[Category: Large Structures]]
+[[Category: Chang CY]]
+[[Category: Cheng T]]
+[[Category: Hsiao PY]]
+[[Category: Kuo YM]]
+[[Category: Wang M]]
+[[Category: Wang N]]

9vex: Difference between revisions

Latest revision as of 05:08, 27 May 2026

Crystal structure of CpaO in complex with beta-CPA

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Function

References

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