5mpt
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the citrinin polyketide synthase CMeT domain== | |
| + | <StructureSection load='5mpt' size='340' side='right'caption='[[5mpt]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5mpt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Monascus_purpureus Monascus purpureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MPT 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]] 1.648Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=5mpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mpt OCA], [https://pdbe.org/5mpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mpt RCSB], [https://www.ebi.ac.uk/pdbsum/5mpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mpt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CITS_MONPU CITS_MONPU] Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of the mycotoxin citrinin, a hepato-nephrotoxic compound to humans due to inhibition of respiration complex III (PubMed:16000748, PubMed:19012408, PubMed:19111642, PubMed:27913218, PubMed:28238725). The pathway begins with the synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT) from successive condensations of 4 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit (PubMed:28238725). Release of the keto-aldehyde intermediate is consistent with the presence of the C-terminal reductive release domain (PubMed:28238725). The exact catalytic role of the hydrolase mpl1 remains mysterious, although it is clear that it increases the productivity of the PKS and performs the earliest non-PKS step during citrinin biosynthesis (PubMed:27913218). Mpl2 then catalyzes the oxidation of the C-12 methyl of the ketone intermediate to an alcohol intermediate which is further oxidized by the oxidoreductase mpl7 to produce a bisaldehyde intermediate (PubMed:27913218). The fourth catalytic step is catalyzed by the mpl4 aldehyde dehydrogenase (PubMed:27913218). The final transformation is the reduction of C-3 by mpl6 to provide the chemically stable citrinin nucleus (PubMed:27913218).<ref>PMID:16000748</ref> <ref>PMID:19012408</ref> <ref>PMID:19111642</ref> <ref>PMID:27913218</ref> <ref>PMID:28238725</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fungal polyketide synthases (PKSs) are large, multidomain enzymes that biosynthesize a wide range of natural products. A hallmark of these megasynthases is the iterative use of catalytic domains to extend and modify a series of enzyme-bound intermediates. A subset of these iterative PKSs (iPKSs) contains a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework. Neither the basis by which only specific positions on the growing intermediate are methylated ("programming") nor the mechanism of methylation are well understood. Domain dissection and reconstitution of PksCT, the fungal non-reducing PKS (NR-PKS) responsible for the first isolable intermediate in citrinin biosynthesis, demonstrates the role of CMeT-catalyzed methylation in precursor elongation and pentaketide formation. The crystal structure of the S-adenosyl-homocysteine (SAH) coproduct-bound PksCT CMeT domain reveals a two-subdomain organization with a novel N-terminal subdomain characteristic of PKS CMeT domains and provides insights into co-factor and ligand recognition. | ||
| - | + | Functional and Structural Analysis of Programmed C-Methylation in the Biosynthesis of the Fungal Polyketide Citrinin.,Storm PA, Herbst DA, Maier T, Townsend CA Cell Chem Biol. 2017 Feb 16. pii: S2451-9456(17)30027-2. doi:, 10.1016/j.chembiol.2017.01.008. PMID:28238725<ref>PMID:28238725</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5mpt" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Monascus purpureus]] | ||
| + | [[Category: Herbst DA]] | ||
| + | [[Category: Maier T]] | ||
| + | [[Category: Storm PA]] | ||
| + | [[Category: Townsend CA]] | ||
Current revision
Structure of the citrinin polyketide synthase CMeT domain
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