View source for 5icf


==Crystal structure of (S)-norcoclaurine 6-O-methyltransferase with S-adenosyl-L-homocysteine and sanguinarine==
<StructureSection load='5icf' size='340' side='right'caption='[[5icf]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5icf]] 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=5ICF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ICF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SAU:13-METHYL[1,3]BENZODIOXOLO[5,6-C][1,3]DIOXOLO[4,5-I]PHENANTHRIDIN-13-IUM'>SAU</scene></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=5icf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5icf OCA], [https://pdbe.org/5icf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5icf RCSB], [https://www.ebi.ac.uk/pdbsum/5icf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5icf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/6OMT_THLFG 6OMT_THLFG] Involved in the biosynthesis of coclaurine, a precursor of benzylisoquinoline alkaloids (PubMed:27232113). Catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine (AdoMet) to the 6-hydroxyl group of norcoclaurine to form coclaurine (PubMed:27232113).<ref>PMID:27232113</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The growing pharmaceutical interest in benzylisoquinoline alkaloids (BIA) coupled with their chemical complexity make metabolic engineering of microbial to create alternative platforms of production increasingly attractive. However, precise knowledge of rate-limiting enzymes and negative feedback inhibition by end-products of BIA metabolism is of paramount importance to this emerging field of synthetic biology. In this work, we report the structural characterization of a (S)-norcoclaurine-6-O-Methyltransferase (6OMT) a key rate-limiting step enzyme involved in the synthesis of reticuline, the final intermediate to be shared between the different end-products of the BIA metabolism, such as morphine, papaverine, berberine and sanguinarine. Four different crystal structures of the enzyme from Thalictrum flavum (Tf 6OMT) were solved: the apoenzyme, the complex with S-adenosyl-L -homocysteine (SAH), the complexes with SAH and the substrate and the complex with SAH and a feedback inhibitor sanguinarine. The Tf 6OMT structural study provides a molecular understanding of its substrate specificity, active site structuration and reaction mechanism. This study also clarifies the inhibition of Tf 6OMT by previously suggested feedback inhibitors. It reveals its high and time dependent sensitivity toward sanguinarine. This article is protected by copyright. All rights reserved.

Crystal structure of norcoclaurine-6-O-methyltransferase a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids.,Robin AY, Giustini C, Graindorge M, Matringe M, Dumas R Plant J. 2016 May 27. doi: 10.1111/tpj.13225. PMID:27232113<ref>PMID:27232113</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5icf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Thalictrum flavum subsp. glaucum]]
[[Category: Dumas R]]
[[Category: Giustini C]]
[[Category: Graindorge M]]
[[Category: Matringe M]]
[[Category: Robin AY]]