View source for 6nev


==FAD-dependent monooxygenase TropB from T. stipitatus Y239F Variant==
<StructureSection load='6nev' size='340' side='right'caption='[[6nev]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nev]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Talaromyces_stipitatus_ATCC_10500 Talaromyces stipitatus ATCC 10500]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NEV 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]] 2.303&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=6nev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nev OCA], [https://pdbe.org/6nev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nev RCSB], [https://www.ebi.ac.uk/pdbsum/6nev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nev ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TROPB_TALSN TROPB_TALSN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Biocatalytic reactions embody many features of ideal chemical transformations, including the potential for impeccable selectivity, high catalytic efficiency, mild reaction conditions and the use of environmentally benign reagents. These advantages have created a demand for biocatalysts that expand the portfolio of complexity-generating reactions available to synthetic chemists. However, the tradeoff that often exists between the substrate scope of a biocatalyst and its selectivity limits the application of enzymes in synthesis. We recently demonstrated that a flavin-dependent monooxygenase, TropB, maintains high levels of site- and stereoselectivity across a range of structurally diverse substrates. Herein, we disclose the structural basis for substrate binding in TropB, which performs a synthetically challenging asymmetric oxidative dearomatization reaction with exquisite site- and stereoselectivity across a range of phenol substrates, providing a foundation for future protein engineering and reaction development efforts. Our hypothesis for substrate binding is informed by a crystal structure of TropB and molecular dynamics simulations with the corresponding computational TropB model and is supported by experimental data. In contrast to canonical class A FAD-dependent monooxygenases in which substrates bind in a protonated form, our data indicate that the phenolate form of the substrate binds in the active site. Furthermore, the substrate position is controlled through twopoint binding of the phenolate oxygen to Arg206 and Tyr239, which are shown to have distinct and essential roles in catalysis. Arg206 is involved in the reduction of the flavin cofactor, suggesting a role in flavin dynamics. Further, QM/MM simulations reveal the interactions that govern the facial selectivity that leads to a highly enantioselective transformation. Thus, the structural origins of the high levels of site-and stereoselectivity observed in reactions of TropB across a range of substrates are elucidated, providing a foundation for future protein engineering and reaction development efforts.

Structural basis for selectivity in flavin-dependent monooxygenase-catalyzed oxidative dearomatization.,Benitez AR, Tweedy S, Baker Dockrey SA, Lukowski AL, Wymore T, Khare D, Brooks CL 3rd, Palfey BA, Smith JL, Narayan ARH ACS Catal. 2019 Apr 5;9(4):3633-3640. doi: 10.1021/acscatal.8b04575. Epub 2019, Mar 25. PMID:31346489<ref>PMID:31346489</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6nev" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Talaromyces stipitatus ATCC 10500]]
[[Category: Baker Dockrey SA]]
[[Category: Khare D]]
[[Category: Lukowski AL]]
[[Category: Narayan ARH]]
[[Category: Palfey BA]]
[[Category: Rodriguez Benitez A]]
[[Category: Smith JL]]
[[Category: Tweedy SE]]
[[Category: Wymore T]]