6ix9: Difference between revisions
New page: '''Unreleased structure''' The entry 6ix9 is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==The structure of LepI C52A in complex with SAM and leporin C== | ||
<StructureSection load='6ix9' size='340' side='right'caption='[[6ix9]], [[Resolution|resolution]] 1.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ix9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_flavus_NRRL3357 Aspergillus flavus NRRL3357]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IX9 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]] 1.776Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B0O:(6R,6aS,10S,10aR)-10-methyl-4-phenyl-6-[(1E)-prop-1-en-1-yl]-2,6,6a,7,8,9,10,10a-octahydro-1H-[2]benzopyrano[4,3-c]pyridin-1-one'>B0O</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=6ix9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ix9 OCA], [https://pdbe.org/6ix9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ix9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ix9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ix9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LEPI_ASPFN LEPI_ASPFN] O-methyltransferase; part of the gene cluster 23 that mediates the biosynthesis of a family of 2-pyridones known as leporins (PubMed:20447271, PubMed:26051490). The hybrid PKS-NRPS synthetase lepA and the enoyl reductase lepG are responsible for fusion of phenylalanine with a hexaketide and subsequent release of the stable tetramic acid precursor, pre-leporin C (PubMed:26051490). Because lepA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase lepG (PubMed:26051490). It is possible that the dehydrogenase lepF also participates in production of pre-leporin C (PubMed:26051490). Cytochrome P450 monooxygenase lepH is then required for the ring expansion step to yield leporin C (PubMed:26051490). Leporin C is then presumably further oxidized by the N-hydroxylase lepD to form leporin B (PubMed:26051490). LepI may possess a function in biosynthesis upstream of lepA (PubMed:26051490). Leporin B is further oxidized in the presence of ferric ion to give the leporin B trimer-iron chelate, but whether or not this reaction is catalyzed by an enzyme in the pathway or by ferric ion is not determined yet (PubMed:26051490).<ref>PMID:26051490</ref> <ref>PMID:20447271</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyses the formation of the 2-pyridone natural product leporin C. Biochemical characterization has shown that LepI can catalyse stereoselective dehydration to yield a reactive (E)-quinone methide that can undergo bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclizations from an ambimodal transition state, as well as a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here, we solve the X-ray crystal structures of SAM-bound LepI and in complex with a substrate analogue, the product leporin C, and a retro-Claisen reaction transition-state analogue to understand the structural basis for the multitude of reactions. Structural and mutational analysis reveals how nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employs H133 and R295, two active-site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact with the substrate, is also proposed. | |||
Structural basis for stereoselective dehydration and hydrogen-bonding catalysis by the SAM-dependent pericyclase LepI.,Cai Y, Hai Y, Ohashi M, Jamieson CS, Garcia-Borras M, Houk KN, Zhou J, Tang Y Nat Chem. 2019 Jul 22. pii: 10.1038/s41557-019-0294-x. doi:, 10.1038/s41557-019-0294-x. PMID:31332284<ref>PMID:31332284</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ix9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus flavus NRRL3357]] | |||
[[Category: Large Structures]] | |||
[[Category: Cai Y]] | |||
[[Category: Hai Y]] | |||
[[Category: Ohashi M]] | |||
[[Category: Tang Y]] | |||
[[Category: Zhou J]] | |||