View source for 6oxj


==X-ray crystal structure of Y140F FtmOx1 bound to Fe(II)==
<StructureSection load='6oxj' size='340' side='right'caption='[[6oxj]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6oxj]] is a 2 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=6OXJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OXJ 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</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=6oxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oxj OCA], [https://pdbe.org/6oxj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oxj RCSB], [https://www.ebi.ac.uk/pdbsum/6oxj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oxj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FTMF_ASPFU FTMF_ASPFU] Catalyzes the conversion of fumitremorgin B to verruculogen.<ref>PMID:19763315</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hydrogen-atom transfer (HAT) from a substrate carbon to an iron(IV)-oxo (ferryl) intermediate initiates a diverse array of enzymatic transformations. For outcomes other than hydroxylation, coupling of the resultant carbon radical and hydroxo ligand (oxygen rebound) must generally be averted. A recent study of FtmOx1, a fungal iron(II)- and 2-(oxo)glutarate-dependent oxygenase that installs the endoperoxide of verruculogen by adding O2 between carbons 21 and 27 of fumitremorgin B, posited that tyrosine (Tyr or Y) 224 serves as HAT intermediary to separate the C21 radical (C21*) and Fe(III)-OH HAT products and prevent rebound. Our reinvestigation of the FtmOx1 mechanism revealed, instead, direct HAT from C21 to the ferryl complex and surprisingly competitive rebound. The C21-hydroxylated (rebound) product, which undergoes deprenylation, predominates when low [O2] slows C21*-O2 coupling in the next step of the endoperoxidation pathway. This pathway culminates with addition of the C21-O-O* peroxyl adduct to olefinic C27 followed by HAT to the C26* from a Tyr. The last step results in sequential accumulation of Tyr radicals, which are suppressed without detriment to turnover by inclusion of the reductant, ascorbate. Replacement of each of four candidates for the proximal C26 H* donor (including Y224) with phenylalanine (F) revealed that only the Y68F variant (i) fails to accumulate the first Tyr* and (ii) makes an altered major product, identifying Y68 as the donor. The implied proximities of C21 to the iron cofactor and C26 to Y68 support a new docking model of the enzyme-substrate complex that is consistent with all available data.

Hydrogen Donation but not Abstraction by a Tyrosine (Y68) during Endoperoxide Installation by Verruculogen Synthase (FtmOx1).,Dunham NP, Del Rio Pantoja JM, Zhang B, Rajakovich LJ, Allen BD, Krebs C, Boal AK, Bollinger JM Jr J Am Chem Soc. 2019 Jun 26;141(25):9964-9979. doi: 10.1021/jacs.9b03567. Epub, 2019 Jun 12. PMID:31117657<ref>PMID:31117657</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6oxj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Aspergillus fumigatus Af293]]
[[Category: Large Structures]]
[[Category: Boal AK]]
[[Category: Dunham NP]]