View source for 6pvh


==Crystal structure of PhqK in complex with paraherquamide K==
<StructureSection load='6pvh' size='340' side='right'caption='[[6pvh]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pvh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Nrrl_746 Nrrl 746]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PVH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=OZ4:(7aS,12S,12aR,13aS)-3,3,12,14,14-pentamethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazol-16-one'>OZ4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">phqK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70095 NRRL 746])</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=6pvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pvh OCA], [http://pdbe.org/6pvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pvh RCSB], [http://www.ebi.ac.uk/pdbsum/6pvh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pvh ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of paraherquamides A and G. Two new paraherquamides (K and L) were isolated from a DeltaphqK strain of Penicillium simplicissimum, and subsequent enzymatic reactions with these compounds generated two additional metabolites, paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing paraherquamide L is the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the paraherquamides and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents.

Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway.,Fraley AE, Caddell Haatveit K, Ye Y, Kelly SP, Newmister SA, Yu F, Williams RM, Smith JL, Houk KN, Sherman DH J Am Chem Soc. 2020 Jan 16. doi: 10.1021/jacs.9b09070. PMID:31904957<ref>PMID:31904957</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pvh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Nrrl 746]]
[[Category: Fraley, A E]]
[[Category: Sherman, D H]]
[[Category: Smith, J L]]
[[Category: Biosynthetic protein]]
[[Category: Flavin]]
[[Category: Monooxygenase]]