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| | <StructureSection load='6oxh' size='340' side='right'caption='[[6oxh]], [[Resolution|resolution]] 1.92Å' scene=''> | | <StructureSection load='6oxh' size='340' side='right'caption='[[6oxh]], [[Resolution|resolution]] 1.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6oxh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OXH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6oxh]] 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=6OXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OXH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Verruculogen_synthase Verruculogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.38 1.14.11.38] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6oxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oxh OCA], [http://pdbe.org/6oxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oxh RCSB], [http://www.ebi.ac.uk/pdbsum/6oxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oxh ProSAT]</span></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=6oxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oxh OCA], [https://pdbe.org/6oxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oxh RCSB], [https://www.ebi.ac.uk/pdbsum/6oxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oxh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FTMF_ASPFU FTMF_ASPFU]] Catalyzes the conversion of fumitremorgin B to verruculogen.<ref>PMID:19763315</ref> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Aspergillus fumigatus Af293]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Verruculogen synthase]]
| + | [[Category: Boal AK]] |
| - | [[Category: Boal, A K]] | + | [[Category: Dunham NP]] |
| - | [[Category: Dunham, N P]] | + | |
| - | [[Category: Deprenylation]]
| + | |
| - | [[Category: Endoperoxidation]]
| + | |
| - | [[Category: Fumitremorgin]]
| + | |
| - | [[Category: Metalloenzyme]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxygenase]]
| + | |
| - | [[Category: Verruculogen]]
| + | |
| Structural highlights
Function
FTMF_ASPFU Catalyzes the conversion of fumitremorgin B to verruculogen.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Steffan N, Grundmann A, Afiyatullov S, Ruan H, Li SM. FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus. Org Biomol Chem. 2009 Oct 7;7(19):4082-7. doi: 10.1039/b908392h. Epub 2009 Aug 6. PMID:19763315 doi:http://dx.doi.org/10.1039/b908392h
- ↑ Dunham NP, Del Rio Pantoja JM, Zhang B, Rajakovich LJ, Allen BD, Krebs C, Boal AK, Bollinger JM Jr. Hydrogen Donation but not Abstraction by a Tyrosine (Y68) during Endoperoxide Installation by Verruculogen Synthase (FtmOx1). J Am Chem Soc. 2019 Jun 26;141(25):9964-9979. doi: 10.1021/jacs.9b03567. Epub, 2019 Jun 12. PMID:31117657 doi:http://dx.doi.org/10.1021/jacs.9b03567
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