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| | <StructureSection load='6vl0' size='340' side='right'caption='[[6vl0]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='6vl0' size='340' side='right'caption='[[6vl0]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vl0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Nitzschia_pungens_f._multiseries Nitzschia pungens f. multiseries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VL0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VL0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vl0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudo-nitzschia_multiseries Pseudo-nitzschia multiseries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VL0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GST:GERANYL+S-THIOLODIPHOSPHATE'>GST</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dabA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37319 Nitzschia pungens f. multiseries])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GST:GERANYL+S-THIOLODIPHOSPHATE'>GST</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vl0 OCA], [http://pdbe.org/6vl0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vl0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vl0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vl0 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=6vl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vl0 OCA], [https://pdbe.org/6vl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vl0 RCSB], [https://www.ebi.ac.uk/pdbsum/6vl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vl0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/DABA_PSEMU DABA_PSEMU] Magnesium-dependent glutamate N-prenyltransferase: part of the gene cluster that mediates the biosynthesis of domoic acid (DA) and derivatives, natural products with neurochemical activity acting as ionotropic glutamate receptor (iGluR) agonists, thus being neurotoxins causing amnesic shellfish poisoning (ASP) (PubMed:30262498). Catalyzes the conversion of L-glutamic acid (L-Glu) to N-geranyl-L-glutamic acid (NGG) in the presence of geranyl diphosphate (GPP) (PubMed:30262498, PubMed:32457155). Also able to catalyze the formation of farnesyl-L-glutamate from farnesyl diphosphate (FPP) (PubMed:32457155). Cannot use dimethylallyl diphosphate (DMAPP) as substrate (PubMed:32457155).<ref>PMID:30262498</ref> <ref>PMID:32457155</ref> |
| - | Prenylation is a common biological reaction in all domains of life wherein prenyl diphosphate donors transfer prenyl groups onto small molecules as well as large proteins. The enzymes that catalyze these reactions are structurally distinct from ubiquitous terpene cyclases that, instead, assemble terpenes via intramolecular rearrangements of a single substrate. Herein, we report the structure and molecular details of a new family of prenyltransferases from marine algae that repurposes the terpene cyclase structural fold for the N-prenylation of glutamic acid during the biosynthesis of the potent neurochemicals domoic acid and kainic acid. We solved the X-ray crystal structure of the prenyltransferase found in domoic acid biosynthesis, DabA, and show distinct active site binding modifications that remodel the canonical magnesium (Mg(2+))-binding motif found in terpene cyclases. We then applied our structural knowledge of DabA and a homologous enzyme from the kainic acid biosynthetic pathway, KabA, to reengineer their isoprene donor specificities (geranyl diphosphate [GPP] versus dimethylallyl diphosphate [DMAPP]) with a single amino acid change. While diatom DabA and seaweed KabA enzymes share a common evolutionary lineage, they are distinct from all other terpene cyclases, suggesting a very distant ancestor to the larger terpene synthase family.
| + | |
| - | | + | |
| - | Algal neurotoxin biosynthesis repurposes the terpene cyclase structural fold into an N-prenyltransferase.,Chekan JR, McKinnie SMK, Noel JP, Moore BS Proc Natl Acad Sci U S A. 2020 May 26. pii: 2001325117. doi:, 10.1073/pnas.2001325117. PMID:32457155<ref>PMID:32457155</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6vl0" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nitzschia pungens f. multiseries]] | + | [[Category: Pseudo-nitzschia multiseries]] |
| - | [[Category: Chekan, J R]] | + | [[Category: Chekan JR]] |
| - | [[Category: Moore, B S]] | + | [[Category: Moore BS]] |
| - | [[Category: Noel, J P]] | + | [[Category: Noel JP]] |
| - | [[Category: Prenyltransferase]]
| + | |
| - | [[Category: Terpene cyclase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
DABA_PSEMU Magnesium-dependent glutamate N-prenyltransferase: part of the gene cluster that mediates the biosynthesis of domoic acid (DA) and derivatives, natural products with neurochemical activity acting as ionotropic glutamate receptor (iGluR) agonists, thus being neurotoxins causing amnesic shellfish poisoning (ASP) (PubMed:30262498). Catalyzes the conversion of L-glutamic acid (L-Glu) to N-geranyl-L-glutamic acid (NGG) in the presence of geranyl diphosphate (GPP) (PubMed:30262498, PubMed:32457155). Also able to catalyze the formation of farnesyl-L-glutamate from farnesyl diphosphate (FPP) (PubMed:32457155). Cannot use dimethylallyl diphosphate (DMAPP) as substrate (PubMed:32457155).[1] [2]
References
- ↑ Brunson JK, McKinnie SMK, Chekan JR, McCrow JP, Miles ZD, Bertrand EM, Bielinski VA, Luhavaya H, Oborník M, Smith GJ, Hutchins DA, Allen AE, Moore BS. Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science. 2018 Sep 28;361(6409):1356-1358. PMID:30262498 doi:10.1126/science.aau0382
- ↑ Chekan JR, McKinnie SMK, Noel JP, Moore BS. Algal neurotoxin biosynthesis repurposes the terpene cyclase structural fold into an N-prenyltransferase. Proc Natl Acad Sci U S A. 2020 May 26. pii: 2001325117. doi:, 10.1073/pnas.2001325117. PMID:32457155 doi:http://dx.doi.org/10.1073/pnas.2001325117
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