5non: Difference between revisions

Latest revision as of 13:16, 15 November 2023

Structure of truncated Norcoclaurine Synthase from Thalictrum flavum with product mimic

Structural highlights

5non is a 3 chain structure with sequence from Thalictrum flavum subsp. glaucum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.85Å
Ligands:	93H
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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:https://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:https://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:https://dx.doi.org/10.1042/BJ20080306
↑ Lichman BR, Sula A, Pesnot T, Hailes HC, Ward JM, Keep NH. Structural Evidence for the Dopamine-First Mechanism of Norcoclaurine Synthase. Biochemistry. 2017 Sep 20. doi: 10.1021/acs.biochem.7b00769. PMID:28915025 doi:https://dx.doi.org/10.1021/acs.biochem.7b00769

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OCA

[1] 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:https://dx.doi.org/10.1021/bi700752n

[2] 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:https://dx.doi.org/10.1016/j.pep.2007.07.010

[3] 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:https://dx.doi.org/10.1042/BJ20080306

[4] Lichman BR, Sula A, Pesnot T, Hailes HC, Ward JM, Keep NH. Structural Evidence for the Dopamine-First Mechanism of Norcoclaurine Synthase. Biochemistry. 2017 Sep 20. doi: 10.1021/acs.biochem.7b00769. PMID:28915025 doi:https://dx.doi.org/10.1021/acs.biochem.7b00769

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='5non' size='340' side='right'caption='[[5non]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5non]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NON OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NON FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5non]] is a 3 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=5NON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NON FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=93H:4-[2-[2-(4-methoxyphenyl)ethylamino]ethyl]benzene-1,2-diol'>93H</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]] 1.85&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5n8q|5n8q]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=93H:4-[2-[2-(4-methoxyphenyl)ethylamino]ethyl]benzene-1,2-diol'>93H</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5non FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5non OCA], [https://pdbe.org/5non PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5non RCSB], [https://www.ebi.ac.uk/pdbsum/5non PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5non ProSAT]</span></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=5non FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5non OCA], [http://pdbe.org/5non PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5non RCSB], [http://www.ebi.ac.uk/pdbsum/5non PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5non ProSAT]</span></td></tr>
 </table>
 == 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 ==
@@ Line 25: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Hailes, H C]]
+[[Category: Thalictrum flavum subsp. glaucum]]
-[[Category: Keep, N H]]
+[[Category: Hailes HC]]
-[[Category: Lichman, B R]]
+[[Category: Keep NH]]
-[[Category: Pesnot, T]]
+[[Category: Lichman BR]]
-[[Category: Sula, A]]
+[[Category: Pesnot T]]
-[[Category: Ward, J M]]
+[[Category: Sula A]]
-[[Category: Dopamine]]
+[[Category: Ward JM]]
-[[Category: Lyase]]
-[[Category: Pictet spengler condensation]]

5non: Difference between revisions

Latest revision as of 13:16, 15 November 2023

Structure of truncated Norcoclaurine Synthase from Thalictrum flavum with product mimic

Structural highlights

Function

Publication Abstract from PubMed

References

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