|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6cy8' size='340' side='right'caption='[[6cy8]], [[Resolution|resolution]] 2.73Å' scene=''> | | <StructureSection load='6cy8' size='340' side='right'caption='[[6cy8]], [[Resolution|resolution]] 2.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cy8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Marm1 Marm1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CY8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CY8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cy8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Marinomonas_mediterranea_MMB-1 Marinomonas mediterranea MMB-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CY8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CY8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PNS:4-PHOSPHOPANTETHEINE'>PNS</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]] 2.729Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Marme_4091 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=717774 MARM1]), Marme_4088 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=717774 MARM1])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PNS:4-PHOSPHOPANTETHEINE'>PNS</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Short-chain_acyl-CoA_dehydrogenase Short-chain acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.8.1 1.3.8.1] </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=6cy8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cy8 OCA], [https://pdbe.org/6cy8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cy8 RCSB], [https://www.ebi.ac.uk/pdbsum/6cy8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cy8 ProSAT]</span></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=6cy8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cy8 OCA], [http://pdbe.org/6cy8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cy8 RCSB], [http://www.ebi.ac.uk/pdbsum/6cy8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cy8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/F2K077_MARM1 F2K077_MARM1] |
| - | Sequential enzymatic reactions on substrates tethered to carrier proteins (CPs) generates thiotemplated building blocks that are then delivered to non-ribosomal peptide synthetases (NRPSs) to generate peptidic natural products. The underlying diversity of these thiotemplated building blocks is the principal driver of the chemical diversity of NRPS-derived natural products. Structural insights into recognition of CPs by tailoring enzymes that generate these building blocks are sparse. Here we present the crystal structure of a flavin-dependent prolyl oxidase that furnishes thiotemplated pyrrole as the product, in complex with its cognate CP in the holo- and product bound states. The thiotemplated pyrrole is an intermediate that is well represented in natural product biosynthetic pathways. Our results delineate the interactions between the CP and the oxidase, while also providing insights into the stereospecificity of the enzymatic oxidation of the prolyl heterocycle to the aromatic pyrrole. Biochemical validation of the interaction between the CP and the oxidase demonstrates that NRPSs recognize and bind to their CPs using interactions quite different to that from fatty acid and polyketide biosynthetic enzymes. Our results posit that structural diversity in natural product biosynthesis can be, and is, derived from subtle modifications of primary metabolic enzymes.
| + | |
| - | | + | |
| - | Insights into thiotemplated pyrrole biosynthesis gained by crystal structure of flavin-dependent oxidase in complex with carrier protein.,Thapa HR, Robbins JM, Moore BS, Agarwal V Biochemistry. 2019 Jan 8. doi: 10.1021/acs.biochem.8b01177. PMID:30620182<ref>PMID:30620182</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6cy8" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]] | | *[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Marm1]] | + | [[Category: Marinomonas mediterranea MMB-1]] |
| - | [[Category: Short-chain acyl-CoA dehydrogenase]]
| + | [[Category: Agarwal V]] |
| - | [[Category: Agarwal, V]] | + | |
| - | [[Category: Acyl carrier protein]]
| + | |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: Fad-dependent enzyme]]
| + | |
| - | [[Category: Natural product biosynthesis]]
| + | |
