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| | <StructureSection load='6rp3' size='340' side='right'caption='[[6rp3]], [[Resolution|resolution]] 1.81Å' scene=''> | | <StructureSection load='6rp3' size='340' side='right'caption='[[6rp3]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rp3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RP3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rp3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thalictrum_flavum_subsp._glaucum Thalictrum flavum subsp. glaucum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RP3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KCZ:4-[2-[[(2~{R})-2-phenylpropyl]amino]ethyl]benzene-1,2-diol'>KCZ</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]] 1.81Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(S)-norcoclaurine_synthase (S)-norcoclaurine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.78 4.2.1.78] </span></td></tr>
| + | <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=KCZ:4-[2-[[(2~{R})-2-phenylpropyl]amino]ethyl]benzene-1,2-diol'>KCZ</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=6rp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rp3 OCA], [http://pdbe.org/6rp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rp3 RCSB], [http://www.ebi.ac.uk/pdbsum/6rp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rp3 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=6rp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rp3 OCA], [https://pdbe.org/6rp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rp3 RCSB], [https://www.ebi.ac.uk/pdbsum/6rp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rp3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCS_THLFG NCS_THLFG]] Involved in the biosynthesis of the common precursor of all benzylisoquinoline alkaloids such as morphine, sanguinarine, codeine or berberine. Condenses dopamine and 4-hydroxyphenylacetaldehyde.<ref>PMID:17696451</ref> <ref>PMID:17900926</ref> <ref>PMID:18384289</ref> | + | [https://www.uniprot.org/uniprot/NCS_THLFG NCS_THLFG] Involved in the biosynthesis of the common precursor of all benzylisoquinoline alkaloids such as morphine, sanguinarine, codeine or berberine. Condenses dopamine and 4-hydroxyphenylacetaldehyde.<ref>PMID:17696451</ref> <ref>PMID:17900926</ref> <ref>PMID:18384289</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Norcoclaurine synthase (NCS) is a Pictet-Spenglerase that catalyzes the first key step in plant benzylisoquinoline alkaloid metabolism, a compound family that includes bioactive natural products such as morphine. The enzyme has also shown great potential as a biocatalyst for the formation of chiral isoquinolines. Here we present new high-resolution X-ray crystallography data describing Thalictrum flavum NCS bound to a mechanism-inspired ligand. The structure supports two key features of the NCS "dopamine-first" mechanism: the binding of dopamine catechol to Lys-122 and the position of the carbonyl substrate binding site at the active site entrance. The catalytically vital residue Glu-110 occupies a previously unobserved ligand-bound conformation that may be catalytically significant. The potential roles of inhibitory binding and alternative amino acid conformations in the mechanism have also been revealed. This work significantly advances our understanding of the NCS mechanism and will aid future efforts to engineer the substrate scope and catalytic properties of this useful biocatalyst.
| + | |
| - | | + | |
| - | Structural Evidence for the Dopamine-First Mechanism of Norcoclaurine Synthase.,Lichman BR, Sula A, Pesnot T, Hailes HC, Ward JM, Keep NH Biochemistry. 2017 Sep 20. doi: 10.1021/acs.biochem.7b00769. PMID:28915025<ref>PMID:28915025</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6rp3" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Keep, N H]] | + | [[Category: Thalictrum flavum subsp. glaucum]] |
| - | [[Category: Roddan, R]] | + | [[Category: Keep NH]] |
| - | [[Category: Sula, A]] | + | [[Category: Roddan R]] |
| - | [[Category: Biotransformation]] | + | [[Category: Sula A]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Tetrahydroisoquinoline synthase]]
| + | |
| Structural highlights
Function
NCS_THLFG Involved in the biosynthesis of the common precursor of all benzylisoquinoline alkaloids such as morphine, sanguinarine, codeine or berberine. Condenses dopamine and 4-hydroxyphenylacetaldehyde.[1] [2] [3]
References
- ↑ Luk LY, Bunn S, Liscombe DK, Facchini PJ, Tanner ME. Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: an enzymatic Pictet-Spengler reaction. Biochemistry. 2007 Sep 4;46(35):10153-61. Epub 2007 Aug 15. PMID:17696451 doi:http://dx.doi.org/10.1021/bi700752n
- ↑ Berkner H, Engelhorn J, Liscombe DK, Schweimer K, Wohrl BM, Facchini PJ, Rosch P, Matecko I. High-yield expression and purification of isotopically labeled norcoclaurine synthase, a Bet v 1-homologous enzyme, from Thalictrum flavum for NMR studies. Protein Expr Purif. 2007 Dec;56(2):197-204. Epub 2007 Aug 24. PMID:17900926 doi:http://dx.doi.org/10.1016/j.pep.2007.07.010
- ↑ Berkner H, Schweimer K, Matecko I, Rosch P. Conformation, catalytic site, and enzymatic mechanism of the PR10 allergen-related enzyme norcoclaurine synthase. Biochem J. 2008 Jul 15;413(2):281-90. doi: 10.1042/BJ20080306. PMID:18384289 doi:http://dx.doi.org/10.1042/BJ20080306
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