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| | <StructureSection load='4r82' size='340' side='right'caption='[[4r82]], [[Resolution|resolution]] 1.66Å' scene=''> | | <StructureSection load='4r82' size='340' side='right'caption='[[4r82]], [[Resolution|resolution]] 1.66Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_globisporus"_krasil'nikov_1941 "actinomyces globisporus" krasil'nikov 1941]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R82 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_globisporus Streptomyces globisporus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R82 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | + | </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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4r82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r82 OCA], [https://pdbe.org/4r82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r82 RCSB], [https://www.ebi.ac.uk/pdbsum/4r82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r82 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oo2|4oo2]], [[4hx6|4hx6]]</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=4r82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r82 OCA], [http://pdbe.org/4r82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r82 RCSB], [http://www.ebi.ac.uk/pdbsum/4r82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r82 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SGCE6_STRGL SGCE6_STRGL] Reductase component of a two-component system involved in the biosynthesis of the enediyne antitumor antibiotic C-1027 (PubMed:18426211, PubMed:19817865). SgcE6 provides the FADH(2) required by both the halogenase SgcC3 and the monooxygenase SgcC through free diffusion (PubMed:18426211, PubMed:19817865). Accepts only NADH and FAD as substrates (PubMed:19817865).<ref>PMID:18426211</ref> <ref>PMID:19817865</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: Actinomyces globisporus krasil'nikov 1941]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Babnigg, G]] | + | [[Category: Streptomyces globisporus]] |
| - | [[Category: Bigelow, L]] | + | [[Category: Babnigg G]] |
| - | [[Category: Bingman, C A]] | + | [[Category: Bigelow L]] |
| - | [[Category: Clancy, S]] | + | [[Category: Bingman CA]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Clancy S]] |
| - | [[Category: Lohman, J R]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Lohman JR]] |
| - | [[Category: Ma, M]] | + | [[Category: Ma M]] |
| - | [[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]
| + | [[Category: Phillips Jr GN]] |
| - | [[Category: Phillips, G N]] | + | [[Category: Shen B]] |
| - | [[Category: Shen, B]] | + | [[Category: Tan K]] |
| - | [[Category: Tan, K]] | + | [[Category: Yennamalli R]] |
| - | [[Category: Yennamalli, R]] | + | |
| - | [[Category: Enzyme discovery for natural product biosynthesis]]
| + | |
| - | [[Category: Mcsg]]
| + | |
| - | [[Category: Natpro]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| Structural highlights
4r82 is a 2 chain structure with sequence from Streptomyces globisporus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
SGCE6_STRGL Reductase component of a two-component system involved in the biosynthesis of the enediyne antitumor antibiotic C-1027 (PubMed:18426211, PubMed:19817865). SgcE6 provides the FADH(2) required by both the halogenase SgcC3 and the monooxygenase SgcC through free diffusion (PubMed:18426211, PubMed:19817865). Accepts only NADH and FAD as substrates (PubMed:19817865).[1] [2]
Publication Abstract from PubMed
C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-beta-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-beta-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 A resolution, respectively. SgcE6 shares a similar beta-barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few other known FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.
Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus.,Chang CY, Lohman JR, Cao H, Tan K, Rudolf JD, Ma M, Xu W, Bingman CA, Yennamalli RM, Bigelow L, Babnigg G, Yan X, Joachimiak A, Phillips GN Jr, Shen B Biochemistry. 2016 Sep 13;55(36):5142-54. doi: 10.1021/acs.biochem.6b00713. Epub , 2016 Sep 1. PMID:27560143[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin S, Van Lanen SG, Shen B. Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. J Am Chem Soc. 2008 May 21;130(20):6616-23. doi: 10.1021/ja710601d. Epub 2008 Apr, 22. PMID:18426211 doi:http://dx.doi.org/10.1021/ja710601d
- ↑ Van Lanen SG, Lin S, Horsman GP, Shen B. Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. FEMS Microbiol Lett. 2009 Nov;300(2):237-41. doi:, 10.1111/j.1574-6968.2009.01802.x. Epub 2009 Sep 27. PMID:19817865 doi:http://dx.doi.org/10.1111/j.1574-6968.2009.01802.x
- ↑ Chang CY, Lohman JR, Cao H, Tan K, Rudolf JD, Ma M, Xu W, Bingman CA, Yennamalli RM, Bigelow L, Babnigg G, Yan X, Joachimiak A, Phillips GN Jr, Shen B. Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus. Biochemistry. 2016 Sep 13;55(36):5142-54. doi: 10.1021/acs.biochem.6b00713. Epub , 2016 Sep 1. PMID:27560143 doi:http://dx.doi.org/10.1021/acs.biochem.6b00713
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