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| | <StructureSection load='5kn4' size='340' side='right'caption='[[5kn4]], [[Resolution|resolution]] 1.99Å' scene=''> | | <StructureSection load='5kn4' size='340' side='right'caption='[[5kn4]], [[Resolution|resolution]] 1.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kn4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Thlfg Thlfg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KN4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kn4]] is a 2 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=5KN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KN4 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5koc|5koc]], [[5kok|5kok]], [[5kpc|5kpc]], [[5kpg|5kpg]]</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]] 1.99Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pavine_N-methyltransferase Pavine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.300 2.1.1.300] </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=5kn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kn4 OCA], [https://pdbe.org/5kn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kn4 RCSB], [https://www.ebi.ac.uk/pdbsum/5kn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kn4 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=5kn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kn4 OCA], [http://pdbe.org/5kn4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kn4 RCSB], [http://www.ebi.ac.uk/pdbsum/5kn4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kn4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PNMT_THLFG PNMT_THLFG] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pavine N-methyltransferase]] | + | [[Category: Thalictrum flavum subsp. glaucum]] |
| - | [[Category: Thlfg]]
| + | [[Category: Chen X]] |
| - | [[Category: Chen, X]] | + | [[Category: Eugenio L]] |
| - | [[Category: Eugenio, L]] | + | [[Category: Facchini PJ]] |
| - | [[Category: Facchini, P J]] | + | [[Category: Hoffarth E]] |
| - | [[Category: Hoffarth, E]] | + | [[Category: Morris J]] |
| - | [[Category: Morris, J]] | + | [[Category: Ng KKS]] |
| - | [[Category: Ng, K K.S]] | + | [[Category: Savtchouk J]] |
| - | [[Category: Savtchouk, J]] | + | [[Category: Torres MA]] |
| - | [[Category: Torres, M A]] | + | |
| - | [[Category: Benzylisoquinoline alkaloid biosynthesis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PNMT_THLFG
Publication Abstract from PubMed
Benzylisoquinoline alkaloids (BIAs) are produced in a wide variety of plants and include many common analgesic, antitussive and anticancer compounds. Several members of a distinct family of S-adenosylmethionine (SAM)-dependent N-methyltransferases (NMTs) play critical roles BIA biosynthesis, but, the molecular basis of substrate recognition and catalysis are not known for NMTs involved in BIA metabolism. To address this issue, the crystal structure of pavine NMT (PavNMT) from Thalictrum flavum was solved using selenomethionine-substituted protein (dmin = 2.8 A). Additional structures were determined for the native protein (dmin = 2.0 A), as well as binary complexes with SAM (dmin = 2.3 A) or the reaction product S-adenosylhomocysteine (SAH) (dmin = 1.6 A). The structure of a complex with SAH and two molecules of tetrahydropapaverine (THP, one as the S conformer and a second in the R configuration) (dmin = 1.8 A) revealed key features of substrate recognition. PavNMT converted racemic THP to laudanosine, but the enzyme showed a preference for (+/-)-pavine and (S)-reticuline as substrates. These structures suggest the involvement of highly conserved residues at the active site. Mutagenesis of three residues near the methyl group of SAM and the nitrogen atom of the alkaloid acceptor decreased enzyme activity without disrupting the structure of the protein. The binding site for THP provides a framework for understanding substrate specificity amongst numerous NMTs involved in the biosynthesis of BIAs and other specialized metabolites. This information will facilitate metabolic engineering efforts aimed at producing medicinally important compounds in heterologous systems such as yeast.
Structural and Functional Studies of Pavine N-Methyltransferase from Thalictrum flavum Reveal Novel Insights into Substrate Recognition and Catalytic Mechanism.,Torres MA, Hoffarth E, Eugenio L, Savtchouk J, Chen X, Morris J, Facchini PJ, Ng KK J Biol Chem. 2016 Aug 29. pii: jbc.M116.747261. PMID:27573242[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Torres MA, Hoffarth E, Eugenio L, Savtchouk J, Chen X, Morris J, Facchini PJ, Ng KK. Structural and Functional Studies of Pavine N-Methyltransferase from Thalictrum flavum Reveal Novel Insights into Substrate Recognition and Catalytic Mechanism. J Biol Chem. 2016 Aug 29. pii: jbc.M116.747261. PMID:27573242 doi:http://dx.doi.org/10.1074/jbc.M116.747261
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