4hb9
From Proteopedia
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<StructureSection load='4hb9' size='340' side='right'caption='[[4hb9]], [[Resolution|resolution]] 1.93Å' scene=''> | <StructureSection load='4hb9' size='340' side='right'caption='[[4hb9]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4hb9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[4hb9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Photorhabdus_laumondii_subsp._laumondii_TTO1 Photorhabdus laumondii subsp. laumondii TTO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HB9 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <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=4hb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hb9 OCA], [https://pdbe.org/4hb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hb9 RCSB], [https://www.ebi.ac.uk/pdbsum/4hb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hb9 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=4hb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hb9 OCA], [https://pdbe.org/4hb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hb9 RCSB], [https://www.ebi.ac.uk/pdbsum/4hb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hb9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q7N4T1_PHOLL Q7N4T1_PHOLL] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Members of the gammaproteobacterial Photorhabdus genus share mutualistic relationships with Heterorhabditis nematodes, and the pairs infect a wide swath of insect larvae. Photorhabdus species produce a family of stilbenes, with two major components being 3,5-dihydroxy-4-isopropyl-trans-stilbene (compound 1) and its stilbene epoxide (compound 2). This family of molecules harbors antimicrobial and immunosuppressive activities, and its pathway is responsible for producing a nematode "food signal" involved in nematode development. However, stilbene epoxidation biosynthesis and its biological roles remain unknown. Here, we identified an orphan protein (Plu2236) from Photorhabdus luminescens that catalyzes stilbene epoxidation. Structural, mutational, and biochemical analyses confirmed the enzyme adopts a fold common to FAD-dependent monooxygenases, contains a tightly bound FAD prosthetic group, and is required for the stereoselective epoxidation of compounds 1 and 2. The epoxidase gene was dispensable in a nematode-infective juvenile recovery assay, indicating the oxidized compound is not required for the food signal. The epoxide exhibited reduced cytotoxicity toward its producer, suggesting this may be a natural route for intracellular detoxification. In an insect infection model, we also observed two stilbene-derived metabolites that were dependent on the epoxidase. NMR, computational, and chemical degradation studies established their structures as new stilbene-l-proline conjugates, prolbenes A (compound 3) and B (compound 4). The prolbenes lacked immunosuppressive and antimicrobial activities compared with their stilbene substrates, suggesting a metabolite attenuation mechanism in the animal model. Collectively, our studies provide a structural view for stereoselective stilbene epoxidation and functionalization in an invertebrate animal infection model and provide new insights into stilbene cellular detoxification. | Members of the gammaproteobacterial Photorhabdus genus share mutualistic relationships with Heterorhabditis nematodes, and the pairs infect a wide swath of insect larvae. Photorhabdus species produce a family of stilbenes, with two major components being 3,5-dihydroxy-4-isopropyl-trans-stilbene (compound 1) and its stilbene epoxide (compound 2). This family of molecules harbors antimicrobial and immunosuppressive activities, and its pathway is responsible for producing a nematode "food signal" involved in nematode development. However, stilbene epoxidation biosynthesis and its biological roles remain unknown. Here, we identified an orphan protein (Plu2236) from Photorhabdus luminescens that catalyzes stilbene epoxidation. Structural, mutational, and biochemical analyses confirmed the enzyme adopts a fold common to FAD-dependent monooxygenases, contains a tightly bound FAD prosthetic group, and is required for the stereoselective epoxidation of compounds 1 and 2. The epoxidase gene was dispensable in a nematode-infective juvenile recovery assay, indicating the oxidized compound is not required for the food signal. The epoxide exhibited reduced cytotoxicity toward its producer, suggesting this may be a natural route for intracellular detoxification. In an insect infection model, we also observed two stilbene-derived metabolites that were dependent on the epoxidase. NMR, computational, and chemical degradation studies established their structures as new stilbene-l-proline conjugates, prolbenes A (compound 3) and B (compound 4). The prolbenes lacked immunosuppressive and antimicrobial activities compared with their stilbene substrates, suggesting a metabolite attenuation mechanism in the animal model. Collectively, our studies provide a structural view for stereoselective stilbene epoxidation and functionalization in an invertebrate animal infection model and provide new insights into stilbene cellular detoxification. | ||
| - | Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis.,Park HB, Sampathkumar P, Perez CE, Lee JH, Tran J, Bonanno JB, Hallem EA, Almo SC, Crawford JM J Biol Chem. 2017 Apr 21;292(16):6680-6694. doi: 10.1074/jbc.M116.762542. Epub, 2017 Feb 28. PMID:28246174<ref>PMID:28246174</ref> | + | Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis.,Park HB, Sampathkumar P, Perez CE, Lee JH, Tran J, Bonanno JB, Hallem EA, Almo SC, Crawford JM J Biol Chem. 2017 Apr 21;292(16):6680-6694. doi: 10.1074/jbc.M116.762542. Epub , 2017 Feb 28. PMID:28246174<ref>PMID:28246174</ref> |
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> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Photorhabdus laumondii subsp. laumondii TTO1]] |
| - | [[Category: Almo | + | [[Category: Almo SC]] |
| - | + | [[Category: Sampathkumar P]] | |
| - | [[Category: Sampathkumar | + | |
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Current revision
Crystal structure of a putative FAD containing monooxygenase from Photorhabdus luminescens subsp. laumondii TTO1 (Target PSI-012791)
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