View source for 9vex


==Crystal structure of CpaO in complex with beta-CPA==
<StructureSection load='9vex' size='340' side='right'caption='[[9vex]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
== 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>
</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>
<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>
<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>
</table>
== Function ==
[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> 
== References ==
<references/>
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</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]]