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| | ==Structure of PvcB, an Fe, alpha-ketoglutarate dependent oxygenase from an isonitrile synthetic pathway== | | ==Structure of PvcB, an Fe, alpha-ketoglutarate dependent oxygenase from an isonitrile synthetic pathway== |
| - | <StructureSection load='4ylm' size='340' side='right' caption='[[4ylm]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='4ylm' size='340' side='right'caption='[[4ylm]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ylm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YLM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ylm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAK Pseudomonas aeruginosa PAK]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YLM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.05Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eat|3eat]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4ylm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ylm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ylm RCSB], [http://www.ebi.ac.uk/pdbsum/4ylm PDBsum]</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=4ylm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ylm OCA], [https://pdbe.org/4ylm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ylm RCSB], [https://www.ebi.ac.uk/pdbsum/4ylm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ylm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PVCB_PSEAE PVCB_PSEAE] Involved in the biosynthesis of paerucumarin, a cyclized isocyano derivative of tyrosine (PubMed:18689486, PubMed:18824174). Catalyzes the 2-oxoglutarate-dependent oxidation of tyrosine isonitrile (PubMed:25866990).<ref>PMID:18689486</ref> <ref>PMID:18824174</ref> <ref>PMID:25866990</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ylm" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gulick, A M]] | + | [[Category: Large Structures]] |
| - | [[Category: Lippa, G M]] | + | [[Category: Pseudomonas aeruginosa PAK]] |
| - | [[Category: Tipton, P A]] | + | [[Category: Gulick AM]] |
| - | [[Category: Zhu, J]] | + | [[Category: Lippa GM]] |
| - | [[Category: Fe/a-ketoglutarate]] | + | [[Category: Tipton PA]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Zhu J]] |
| - | [[Category: Oxygenase]]
| + | |
| Structural highlights
Function
PVCB_PSEAE Involved in the biosynthesis of paerucumarin, a cyclized isocyano derivative of tyrosine (PubMed:18689486, PubMed:18824174). Catalyzes the 2-oxoglutarate-dependent oxidation of tyrosine isonitrile (PubMed:25866990).[1] [2] [3]
Publication Abstract from PubMed
Many bacteria produce isonitrile-containing natural products that are derived from aromatic amino acids. The synthetic clusters that control biosynthesis most commonly encode two enzymes, designated PvcA and PvcB, as well as additional enzymes that direct synthesis of the natural product. The PvcA enzyme installs the isonitrile moiety at the amino group of either tyrosine or tryptophan, as dictated by the particular pathway. The common pathway intermediate produced by PvcA is directed toward different ultimate products by PvcB, a member of the family of Fe(2+), alpha-ketoglutarate-dependent oxygenases. To continue our investigation of the structural and functional properties of the isonitrile biosynthetic pathways, we present here a study of the PvcB homologues from three organisms. Two pathways, derived from Pseudomonas aeruginosa and Xenorhabdus nematophila, produce known products. A third PvcB homologue from Erwinia amylovora is part of an uncharacterized pathway. Our results demonstrate the diversity of reactions catalyzed. Although all PvcB enzymes catalyze the hydroxylation of the tyrosine isonitrile substrate, the elimination of the hydroxyl in Pseudomonas and Erwinia is driven by deprotonation at Calpha, resulting in the initial production of an unsaturated tyrosine isonitrile product that then cyclizes to a coumarin derivative. PvcB from Xenorhabdus, in contrast, catalyzes the same oxygenation, but loss of the hydroxyl group is accompanied by decarboxylation of the intermediate. Steady-state kinetic analysis of the three reactions and a docking model for the binding of the tyrosine isonitrile substrate in the PvcB active site highlight subtle differences between the PvcB homologues.
Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile-Containing Natural Products.,Zhu J, Lippa GM, Gulick AM, Tipton PA Biochemistry. 2015 Apr 28;54(16):2659-69. doi: 10.1021/acs.biochem.5b00255. Epub , 2015 Apr 20. PMID:25866990[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Clarke-Pearson MF, Brady SF. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J Bacteriol. 2008 Oct;190(20):6927-30. PMID:18689486 doi:10.1128/JB.00801-08
- ↑ Drake EJ, Gulick AM. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J Mol Biol. 2008 Dec 5;384(1):193-205. Epub 2008 Sep 19. PMID:18824174 doi:10.1016/j.jmb.2008.09.027
- ↑ Zhu J, Lippa GM, Gulick AM, Tipton PA. Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile-Containing Natural Products. Biochemistry. 2015 Apr 28;54(16):2659-69. doi: 10.1021/acs.biochem.5b00255. Epub , 2015 Apr 20. PMID:25866990 doi:http://dx.doi.org/10.1021/acs.biochem.5b00255
- ↑ Zhu J, Lippa GM, Gulick AM, Tipton PA. Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile-Containing Natural Products. Biochemistry. 2015 Apr 28;54(16):2659-69. doi: 10.1021/acs.biochem.5b00255. Epub , 2015 Apr 20. PMID:25866990 doi:http://dx.doi.org/10.1021/acs.biochem.5b00255
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