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| | <StructureSection load='5oxt' size='340' side='right'caption='[[5oxt]], [[Resolution|resolution]] 1.42Å' scene=''> | | <StructureSection load='5oxt' size='340' side='right'caption='[[5oxt]], [[Resolution|resolution]] 1.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oxt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Agrae Agrae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OXT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OXT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oxt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyclocybe_aegerita Cyclocybe aegerita]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OXT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.42Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2yor|2yor]], [[2yp1|2yp1]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5400 AGRAE])</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=5oxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oxt OCA], [https://pdbe.org/5oxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oxt RCSB], [https://www.ebi.ac.uk/pdbsum/5oxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oxt ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_peroxygenase Unspecific peroxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.2.1 1.11.2.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5oxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oxt OCA], [http://pdbe.org/5oxt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oxt RCSB], [http://www.ebi.ac.uk/pdbsum/5oxt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oxt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/APO1_AGRAE APO1_AGRAE]] Aromatic peroxidase that oxidizes aryl alcohols into the corresponding aldehydes and then into the corresponding benzoic acids. Oxidizes toluene and naphthalene. Catalyzes the regioselective peroxide-dependent hydroxylation of propranolol and diclofenac to 5-hydroxypropranolol and 4'-hydroxydiclofenac. Catalyzes the regioselective peroxide-dependent hydroxylation of naphthalene to 1-naphthol or 2-naphthol via a naphthalene 1,2-oxide intermediate. Catalyzes the regioselective peroxide-dependent oxidation of pyridine to pyridine N-oxide. Halogenates monochlorodimedone and phenol. Oxidizes the sulfer-containing heterocycle dibenzothiophene to yield ring-hydroxylation products and to a lesser extent sulfoxidation products.<ref>PMID:15294788</ref> <ref>PMID:16253244</ref> <ref>PMID:17410351</ref> <ref>PMID:19022254</ref> <ref>PMID:19039585</ref> <ref>PMID:18815784</ref> <ref>PMID:19394224</ref> | + | [https://www.uniprot.org/uniprot/APO1_CYCAE APO1_CYCAE] Aromatic peroxidase that oxidizes aryl alcohols into the corresponding aldehydes and then into the corresponding benzoic acids. Oxidizes toluene and naphthalene. Catalyzes the regioselective peroxide-dependent hydroxylation of propranolol and diclofenac to 5-hydroxypropranolol and 4'-hydroxydiclofenac. Catalyzes the regioselective peroxide-dependent hydroxylation of naphthalene to 1-naphthol or 2-naphthol via a naphthalene 1,2-oxide intermediate. Catalyzes the regioselective peroxide-dependent oxidation of pyridine to pyridine N-oxide. Halogenates monochlorodimedone and phenol. Oxidizes the sulfur-containing heterocycle dibenzothiophene to yield ring-hydroxylation products and to a lesser extent sulfoxidation products.<ref>PMID:15294788</ref> <ref>PMID:16253244</ref> <ref>PMID:17410351</ref> <ref>PMID:18815784</ref> <ref>PMID:19022254</ref> <ref>PMID:19039585</ref> <ref>PMID:19394224</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: Agrae]] | + | [[Category: Cyclocybe aegerita]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Unspecific peroxygenase]]
| + | [[Category: Ramirez-Escudero M]] |
| - | [[Category: Ramirez-Escudero, M]] | + | [[Category: Sanz-Aparicio J]] |
| - | [[Category: Sanz-Aparicio, J]] | + | |
| - | [[Category: Acetate]]
| + | |
| - | [[Category: Agrocybe aegerita]]
| + | |
| - | [[Category: Directed evolution]]
| + | |
| - | [[Category: Heme-thiolate peroxidase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Padai]]
| + | |
| - | [[Category: Upo]]
| + | |
| Structural highlights
5oxt is a 3 chain structure with sequence from Cyclocybe aegerita. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.42Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
APO1_CYCAE Aromatic peroxidase that oxidizes aryl alcohols into the corresponding aldehydes and then into the corresponding benzoic acids. Oxidizes toluene and naphthalene. Catalyzes the regioselective peroxide-dependent hydroxylation of propranolol and diclofenac to 5-hydroxypropranolol and 4'-hydroxydiclofenac. Catalyzes the regioselective peroxide-dependent hydroxylation of naphthalene to 1-naphthol or 2-naphthol via a naphthalene 1,2-oxide intermediate. Catalyzes the regioselective peroxide-dependent oxidation of pyridine to pyridine N-oxide. Halogenates monochlorodimedone and phenol. Oxidizes the sulfur-containing heterocycle dibenzothiophene to yield ring-hydroxylation products and to a lesser extent sulfoxidation products.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Because of their minimal requirements, substrate promiscuity and product selectivity, fungal peroxygenases are now considered to be the jewel in the crown of C-H oxyfunctionalization biocatalysts. In this work, the crystal structure of the first laboratory-evolved peroxygenase expressed by yeast was determined at a resolution of 1.5 A. Notable differences were detected between the evolved and native peroxygenase from Agrocybe aegerita, including the presence of a full N-terminus and a broader heme access channel due to the mutations that accumulated through directed evolution. Further mutagenesis and soaking experiments with a palette of peroxygenative and peroxidative substrates suggested dynamic trafficking through the heme channel as the main driving force for the exceptional substrate promiscuity of peroxygenase. Accordingly, this study provides the first structural evidence at an atomic level regarding the mode of substrate binding for this versatile biocatalyst, which is discussed within a biological and chemical context.
Structural Insights into the Substrate Promiscuity of a Laboratory-Evolved Peroxygenase.,Ramirez-Escudero M, Molina-Espeja P, Gomez de Santos P, Hofrichter M, Sanz-Aparicio J, Alcalde M ACS Chem Biol. 2018 Nov 16. doi: 10.1021/acschembio.8b00500. PMID:30376293[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ullrich R, Nuske J, Scheibner K, Spantzel J, Hofrichter M. Novel haloperoxidase from the agaric basidiomycete Agrocybe aegerita oxidizes aryl alcohols and aldehydes. Appl Environ Microbiol. 2004 Aug;70(8):4575-81. PMID:15294788 doi:http://dx.doi.org/10.1128/AEM.70.8.4575-4581.2004
- ↑ Ullrich R, Hofrichter M. The haloperoxidase of the agaric fungus Agrocybe aegerita hydroxylates toluene and naphthalene. FEBS Lett. 2005 Nov 7;579(27):6247-50. Epub 2005 Oct 19. PMID:16253244 doi:http://dx.doi.org/10.1016/j.febslet.2005.10.014
- ↑ Kluge MG, Ullrich R, Scheibner K, Hofrichter M. Spectrophotometric assay for detection of aromatic hydroxylation catalyzed by fungal haloperoxidase-peroxygenase. Appl Microbiol Biotechnol. 2007 Jul;75(6):1473-8. Epub 2007 Apr 5. PMID:17410351 doi:http://dx.doi.org/10.1007/s00253-007-0942-8
- ↑ Kluge M, Ullrich R, Dolge C, Scheibner K, Hofrichter M. Hydroxylation of naphthalene by aromatic peroxygenase from Agrocybe aegerita proceeds via oxygen transfer from H2O2 and intermediary epoxidation. Appl Microbiol Biotechnol. 2009 Jan;81(6):1071-6. doi: 10.1007/s00253-008-1704-y., Epub 2008 Sep 25. PMID:18815784 doi:http://dx.doi.org/10.1007/s00253-008-1704-y
- ↑ Ullrich R, Dolge C, Kluge M, Hofrichter M. Pyridine as novel substrate for regioselective oxygenation with aromatic peroxygenase from Agrocybe aegerita. FEBS Lett. 2008 Dec 10;582(29):4100-6. doi: 10.1016/j.febslet.2008.11.006. Epub, 2008 Nov 18. PMID:19022254 doi:http://dx.doi.org/10.1016/j.febslet.2008.11.006
- ↑ Aranda E, Kinne M, Kluge M, Ullrich R, Hofrichter M. Conversion of dibenzothiophene by the mushrooms Agrocybe aegerita and Coprinellus radians and their extracellular peroxygenases. Appl Microbiol Biotechnol. 2009 Apr;82(6):1057-66. doi:, 10.1007/s00253-008-1778-6. Epub 2008 Nov 28. PMID:19039585 doi:http://dx.doi.org/10.1007/s00253-008-1778-6
- ↑ Kinne M, Poraj-Kobielska M, Aranda E, Ullrich R, Hammel KE, Scheibner K, Hofrichter M. Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with a fungal peroxygenase. Bioorg Med Chem Lett. 2009 Jun 1;19(11):3085-7. doi: 10.1016/j.bmcl.2009.04.015. , Epub 2009 Apr 9. PMID:19394224 doi:http://dx.doi.org/10.1016/j.bmcl.2009.04.015
- ↑ Ramirez-Escudero M, Molina-Espeja P, Gomez de Santos P, Hofrichter M, Sanz-Aparicio J, Alcalde M. Structural Insights into the Substrate Promiscuity of a Laboratory-Evolved Peroxygenase. ACS Chem Biol. 2018 Nov 16. doi: 10.1021/acschembio.8b00500. PMID:30376293 doi:http://dx.doi.org/10.1021/acschembio.8b00500
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