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| | ==Distinct Monooxygenase and Farnesene Synthase Active Sites in Cytochrome P450 170A1== | | ==Distinct Monooxygenase and Farnesene Synthase Active Sites in Cytochrome P450 170A1== |
| - | <StructureSection load='3el3' size='340' side='right' caption='[[3el3]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='3el3' size='340' side='right'caption='[[3el3]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3el3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_coelicolor"_(muller_1908)_lieske_1921 "actinomyces coelicolor" (muller 1908) lieske 1921]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EL3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EL3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3el3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EL3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EL3:(3S,3AR,6S)-3,7,7,8-TETRAMETHYL-2,3,4,5,6,7-HEXAHYDRO-1H-3A,6-METHANOAZULENE'>EL3</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 3.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dbg|3dbg]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EL3:(3S,3AR,6S)-3,7,7,8-TETRAMETHYL-2,3,4,5,6,7-HEXAHYDRO-1H-3A,6-METHANOAZULENE'>EL3</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=3el3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3el3 OCA], [http://pdbe.org/3el3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3el3 RCSB], [http://www.ebi.ac.uk/pdbsum/3el3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3el3 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=3el3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3el3 OCA], [https://pdbe.org/3el3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3el3 RCSB], [https://www.ebi.ac.uk/pdbsum/3el3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3el3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EIZFM_STRCO EIZFM_STRCO]] Involved in the biosynthesis of the sesquiterpenoid antibiotic albaflavenone. Catalyzes the two-step allylic oxidation of epi-isozizaene to albaflavenone. First carries out a non-stereo-specific oxidation of epi-isozizaene to give a mixture of the albaflavenol epimers ((5R)-albaflavenol and (5S)-albaflavenol), each of which can serve as substrate for the second oxidation to yield albaflavenone. This is quite different from most other P450s which catalyze regio- and stereospecific oxidation. Displays also a farnesene synthase activity with farnesyl diphosphate (FPP) as substrate.<ref>PMID:18234666</ref> <ref>PMID:19858213</ref> | + | [https://www.uniprot.org/uniprot/EIZFM_STRCO EIZFM_STRCO] Involved in the biosynthesis of the sesquiterpenoid antibiotic albaflavenone. Catalyzes the two-step allylic oxidation of epi-isozizaene to albaflavenone. First carries out a non-stereo-specific oxidation of epi-isozizaene to give a mixture of the albaflavenol epimers ((5R)-albaflavenol and (5S)-albaflavenol), each of which can serve as substrate for the second oxidation to yield albaflavenone. This is quite different from most other P450s which catalyze regio- and stereospecific oxidation. Displays also a farnesene synthase activity with farnesyl diphosphate (FPP) as substrate.<ref>PMID:18234666</ref> <ref>PMID:19858213</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Waterman, M R]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhao, B]] | + | [[Category: Streptomyces coelicolor]] |
| - | [[Category: Antibiotic biosynthesis]] | + | [[Category: Waterman MR]] |
| - | [[Category: Cyp170a1]] | + | [[Category: Zhao B]] |
| - | [[Category: Cytochrome p450 oxidoreductase]]
| + | |
| - | [[Category: Farnesene synthase]]
| + | |
| - | [[Category: Heme]]
| + | |
| - | [[Category: Iron]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Streptomyce]]
| + | |
| Structural highlights
Function
EIZFM_STRCO Involved in the biosynthesis of the sesquiterpenoid antibiotic albaflavenone. Catalyzes the two-step allylic oxidation of epi-isozizaene to albaflavenone. First carries out a non-stereo-specific oxidation of epi-isozizaene to give a mixture of the albaflavenol epimers ((5R)-albaflavenol and (5S)-albaflavenol), each of which can serve as substrate for the second oxidation to yield albaflavenone. This is quite different from most other P450s which catalyze regio- and stereospecific oxidation. Displays also a farnesene synthase activity with farnesyl diphosphate (FPP) as substrate.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Albaflavenone synthase (CYP170A1) is a monooxygenase catalyzing the final two steps in the biosynthesis of this antibiotic in the soil bacterium, Streptomyces coelicolor A3(2). Interestingly, CYP170A1 shows no stereo selection forming equal amounts of two albaflavenol epimers, each of which is oxidized in turn to albaflavenone. To explore the structural basis of the reaction mechanism, we have studied the crystal structures of both ligand-free CYP170A1 (2.6 A) and complex of endogenous substrate (epi-isozizaene) with CYP170A1 (3.3 A). The structure of the complex suggests that the proximal epi-isozizaene molecules may bind to the heme iron in two orientations. In addition, much to our surprise, we have found that albaflavenone synthase also has a second, completely distinct catalytic activity corresponding to the synthesis of farnesene isomers from farnesyl diphosphate. Within the cytochrome P450 alpha-helical domain both the primary sequence and x-ray structure indicate the presence of a novel terpene synthase active site that is moonlighting on the P450 structure. This includes signature sequences for divalent cation binding and an alpha-helical barrel. This barrel is unusual because it consists of only four helices rather than six found in all other terpene synthases. Mutagenesis establishes that this barrel is essential for the terpene synthase activity of CYP170A1 but not for the monooxygenase activity. This is the first bifunctional P450 discovered to have another active site moonlighting on it and the first time a terpene synthase active site is found moonlighting on another protein.
Crystal structure of albaflavenone monooxygenase containing a moonlighting terpene synthase active site.,Zhao B, Lei L, Vassylyev DG, Lin X, Cane DE, Kelly SL, Yuan H, Lamb DC, Waterman MR J Biol Chem. 2009 Dec 25;284(52):36711-9. Epub 2009 Oct 26. PMID:19858213[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao B, Lin X, Lei L, Lamb DC, Kelly SL, Waterman MR, Cane DE. Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2). J Biol Chem. 2008 Mar 28;283(13):8183-9. doi: 10.1074/jbc.M710421200. Epub 2008, Jan 30. PMID:18234666 doi:http://dx.doi.org/10.1074/jbc.M710421200
- ↑ Zhao B, Lei L, Vassylyev DG, Lin X, Cane DE, Kelly SL, Yuan H, Lamb DC, Waterman MR. Crystal structure of albaflavenone monooxygenase containing a moonlighting terpene synthase active site. J Biol Chem. 2009 Dec 25;284(52):36711-9. Epub 2009 Oct 26. PMID:19858213 doi:10.1074/jbc.M109.064683
- ↑ Zhao B, Lei L, Vassylyev DG, Lin X, Cane DE, Kelly SL, Yuan H, Lamb DC, Waterman MR. Crystal structure of albaflavenone monooxygenase containing a moonlighting terpene synthase active site. J Biol Chem. 2009 Dec 25;284(52):36711-9. Epub 2009 Oct 26. PMID:19858213 doi:10.1074/jbc.M109.064683
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