View source for 6kjg


==Crystal structure of PsoF==
<StructureSection load='6kjg' size='340' side='right'caption='[[6kjg]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kjg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KJG 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]] 1.99&#8491;</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=6kjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kjg OCA], [https://pdbe.org/6kjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kjg RCSB], [https://www.ebi.ac.uk/pdbsum/6kjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kjg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PSOF_ASPFU PSOF_ASPFU] Dual-functional monooxygenase/methyltransferase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566). The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566). Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).<ref>PMID:24082142</ref> <ref>PMID:24939566</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Biosynthesis of certain fungal polyketide-peptide synthetases involves C-methyltransferase activity that adds one or more S-adenosyl-l-methionine-derived methyl groups to the carbon framework. The previously reported PsoF-MT, the stand-alone C-methyltransferase (MT) from the pseurotin biosynthetic pathway that exists as a domain within a trifunctional didomain enzyme PsoF, was characterized crystallographically and kinetically using mutants with substrate analogs to understand how a trans-acting C-MT works and compare it to known polyketide synthase-associated C-MTs. This study identified key active-site residues involved in catalysis and substrate recognition, which led us to propose the mechanism of C-methylation and substrate specificity determinants in PsoF-MT.

Functional and Structural Analyses of trans C-Methyltransferase in Fungal Polyketide Biosynthesis.,Kishimoto S, Tsunematsu Y, Matsushita T, Hara K, Hashimoto H, Tang Y, Watanabe K Biochemistry. 2019 Sep 24;58(38):3933-3937. doi: 10.1021/acs.biochem.9b00702., Epub 2019 Sep 11. PMID:31486637<ref>PMID:31486637</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kjg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus fumigatus Af293]]
[[Category: Large Structures]]
[[Category: Hara K]]
[[Category: Hashimoto H]]
[[Category: Matsushita T]]
[[Category: Tsunematsu Y]]
[[Category: Watanabe K]]