5w7m

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<StructureSection load='5w7m' size='340' side='right' caption='[[5w7m]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='5w7m' size='340' side='right' caption='[[5w7m]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5w7m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W7M FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5w7m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Penrw Penrw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W7M FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">roqN, gmt, Pc21g15440 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=500485 PENRW])</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=5w7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7m OCA], [http://pdbe.org/5w7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w7m RCSB], [http://www.ebi.ac.uk/pdbsum/5w7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7m ProSAT]</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=5w7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7m OCA], [http://pdbe.org/5w7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w7m RCSB], [http://www.ebi.ac.uk/pdbsum/5w7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7m ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ROQN_PENRW ROQN_PENRW]] Glandicoline B O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the mycotoxin meleagrin (PubMed:22118684, PubMed:23776469). The first stage is catalyzed by the dipeptide synthase roqA which condenses histidine and tryptophan to produce histidyltryptophanyldiketopiperazine (HTD) (PubMed:22118684, PubMed:23776469). HTD is then converted to roquefortine C through two possible pathways (PubMed:23776469). In the first pathway, prenyltransferase roqD transforms HTD to the intermediate roquefortine D, which is in turn converted to roquefortine C by the cytochrome P450 monooxygenase roqR (PubMed:23776469). In the second pathway, HTD is first converted to the intermediate dehydrohistidyltryptophanyldi-ketopiperazine (DHTD) by roqR which is then prenylated by roqD to form roquefortine C (PubMed:23776469). Roquefortine C can be further transformed to meleagrin via three more reactions including oxydation to glandicolin A by roqM, which is further reduced to glandicoline B by roqO (PubMed:23776469). Finally, glandicoline B is converted to meleagrin by the glandicoline B O-methyltransferase roqN (PubMed:22118684, PubMed:23776469). More studies identified further branching and additional metabolites produced by the roquefortine/meleagrin cluster, including roquefortine F, roquefortine L, roquefortine M, roquefortine N and neoxaline (PubMed:24225953).<ref>PMID:22118684</ref> <ref>PMID:23776469</ref> <ref>PMID:24225953</ref>
[[http://www.uniprot.org/uniprot/ROQN_PENRW ROQN_PENRW]] Glandicoline B O-methyltransferase; part of the gene cluster that mediates the biosynthesis of the mycotoxin meleagrin (PubMed:22118684, PubMed:23776469). The first stage is catalyzed by the dipeptide synthase roqA which condenses histidine and tryptophan to produce histidyltryptophanyldiketopiperazine (HTD) (PubMed:22118684, PubMed:23776469). HTD is then converted to roquefortine C through two possible pathways (PubMed:23776469). In the first pathway, prenyltransferase roqD transforms HTD to the intermediate roquefortine D, which is in turn converted to roquefortine C by the cytochrome P450 monooxygenase roqR (PubMed:23776469). In the second pathway, HTD is first converted to the intermediate dehydrohistidyltryptophanyldi-ketopiperazine (DHTD) by roqR which is then prenylated by roqD to form roquefortine C (PubMed:23776469). Roquefortine C can be further transformed to meleagrin via three more reactions including oxydation to glandicolin A by roqM, which is further reduced to glandicoline B by roqO (PubMed:23776469). Finally, glandicoline B is converted to meleagrin by the glandicoline B O-methyltransferase roqN (PubMed:22118684, PubMed:23776469). More studies identified further branching and additional metabolites produced by the roquefortine/meleagrin cluster, including roquefortine F, roquefortine L, roquefortine M, roquefortine N and neoxaline (PubMed:24225953).<ref>PMID:22118684</ref> <ref>PMID:23776469</ref> <ref>PMID:24225953</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Antimicrobial and anti-proliferative meleagrin and oxaline are roquefortine C-derived alkaloids produced by fungi of the genus Penicillium. Tandem O-methylations complete the biosynthesis of oxaline from glandicoline B through meleagrin. Currently, little is known about the role of these methylation patterns in the bioactivity profile of meleagrin and oxaline. To establish the structural and mechanistic basis of methylation in these pathways, crystal structures were determined for two late-stage methyltransferases in the oxaline and meleagrin gene clusters from Penicillium oxalicum and Penicillium chrysogenum. The homologous enzymes OxaG and RoqN were shown to catalyze penultimate hydroxylamine O-methylation to generate meleagrin in vitro. Crystal structures of these enzymes in the presence of methyl donor S-adenosylmethionine revealed an open active site, which lacks an apparent base indicating that catalysis is driven by proximity effects. OxaC was shown to methylate meleagrin to form oxaline in vitro, the terminal pathway product. Crystal structures of OxaC in a pseudo-Michaelis complex containing sinefungin and meleagrin, and in a product complex containing S-adenosyl-homocysteine and oxaline, reveal key active site residues with His313 serving as a base that is activated by Glu369. These data provide structural insights into the enzymatic methylation of these alkaloids that include a rare hydroxylamine oxygen acceptor, and can be used to guide future efforts towards selective derivatization and structural diversification and establishing the role of methylation in bioactivity.
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Unveiling sequential late-stage methyltransferase reactions in the meleagrin/oxaline biosynthetic pathway.,Newmister SA, Romminger S, Schmidt JJ, Williams RM, Smith JL, Berlinck RGS, Sherman DH Org Biomol Chem. 2018 Aug 24. doi: 10.1039/c8ob01565a. PMID:30141817<ref>PMID:30141817</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5w7m" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Penrw]]
[[Category: Berlinck, R G.S]]
[[Category: Berlinck, R G.S]]
[[Category: Newmister, S A]]
[[Category: Newmister, S A]]

Revision as of 10:22, 5 September 2018

Crystal structure of RoqN

5w7m, resolution 1.70Å

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