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| | <StructureSection load='6vdq' size='340' side='right'caption='[[6vdq]], [[Resolution|resolution]] 1.78Å' scene=''> | | <StructureSection load='6vdq' size='340' side='right'caption='[[6vdq]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vdq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_lavendulae"_waksman_and_curtis_1916 "actinomyces lavendulae" waksman and curtis 1916]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VDQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vdq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VDQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</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]] 1.78Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6vdp|6vdp]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sfmD ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1914 "Actinomyces lavendulae" Waksman and Curtis 1916])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-methyl-L-tyrosine_peroxygenase 3-methyl-L-tyrosine peroxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.2.5 1.11.2.5] </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=6vdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vdq OCA], [https://pdbe.org/6vdq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vdq RCSB], [https://www.ebi.ac.uk/pdbsum/6vdq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vdq 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=6vdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vdq OCA], [https://pdbe.org/6vdq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vdq RCSB], [https://www.ebi.ac.uk/pdbsum/6vdq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vdq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SFMD_STRLA SFMD_STRLA]] Heme-containing peroxygenase that mediates the hydroxylation of 3-methyl-L-tyrosine (3-Me-Tyr) into 3-hydroxy-5-methyl-L-tyrosine (3-OH-5-Me-Tyr) in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Involved in biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr), a core structure of saframycin A.<ref>PMID:19494690</ref> <ref>PMID:22187429</ref>
| + | [https://www.uniprot.org/uniprot/SFMD_STRLA SFMD_STRLA] Heme-containing peroxygenase that mediates the hydroxylation of 3-methyl-L-tyrosine (3-Me-Tyr) into 3-hydroxy-5-methyl-L-tyrosine (3-OH-5-Me-Tyr) in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Involved in biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr), a core structure of saframycin A.<ref>PMID:19494690</ref> <ref>PMID:22187429</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 lavendulae waksman and curtis 1916]] | |
| - | [[Category: 3-methyl-L-tyrosine peroxygenase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liu, A]] | + | [[Category: Streptomyces lavendulae]] |
| - | [[Category: Shin, I]] | + | [[Category: Liu A]] |
| - | [[Category: Heme]] | + | [[Category: Shin I]] |
| - | [[Category: Histidine-ligated heme]]
| + | |
| - | [[Category: Hydroxylase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
SFMD_STRLA Heme-containing peroxygenase that mediates the hydroxylation of 3-methyl-L-tyrosine (3-Me-Tyr) into 3-hydroxy-5-methyl-L-tyrosine (3-OH-5-Me-Tyr) in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Involved in biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr), a core structure of saframycin A.[1] [2]
Publication Abstract from PubMed
SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78 A resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attached to the protein with an unusual Hx n HxxxC motif (n approximately 38). This heme cofactor is unique in two respects. It contains a single thioether bond in a cysteine-vinyl link with Cys317, and the ferric heme has two axial protein ligands, i.e., His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry.
A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study.,Shin I, Davis I, Nieves-Merced K, Wang Y, McHardy S, Liu A Chem Sci. 2021 Jan 22;12(11):3984-3998. doi: 10.1039/d0sc06369j. PMID:34163669[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fu CY, Tang MC, Peng C, Li L, He YL, Liu W, Tang GL. Biosynthesis of 3-hydroxy-5-methyl-o-methyltyrosine in the saframycin/ safracin biosynthetic pathway. J Microbiol Biotechnol. 2009 May;19(5):439-46. doi: 10.4014/jmb.0808.484. PMID:19494690 doi:http://dx.doi.org/10.4014/jmb.0808.484
- ↑ Tang MC, Fu CY, Tang GL. Characterization of SfmD as a Heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. J Biol Chem. 2012 Feb 10;287(7):5112-21. doi: 10.1074/jbc.M111.306316. Epub 2011 , Dec 20. PMID:22187429 doi:http://dx.doi.org/10.1074/jbc.M111.306316
- ↑ Shin I, Davis I, Nieves-Merced K, Wang Y, McHardy S, Liu A. A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study. Chem Sci. 2021 Jan 22;12(11):3984-3998. doi: 10.1039/d0sc06369j. PMID:34163669 doi:http://dx.doi.org/10.1039/d0sc06369j
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