5icf

Crystal structure of (S)-norcoclaurine 6-O-methyltransferase with S-adenosyl-L-homocysteine and sanguinarine

spinqualitylabelsall models 5icf, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5icf is a 1 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 1.8Å Ligands: DMS, EDO, K, NA, SAH, SAU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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