6nsd

Tar14, tryptophan C-6 flavin-dependent halogenase (chlorinase) from taromycin biosynthesis

spinqualitylabelsall models 6nsd, resolution 1.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nsd is a 2 chain structure with sequence from Saccharomonospora piscinae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.74Å Ligands: FAD, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function W5VG40_SACPI Publication Abstract from PubMed L-4-Chlorokynurenine (L-4-Cl-Kyn) is a neuropharmaceutical drug candidate in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein we report the unprecedented conversion of L-tryptophan to L-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490. We used genetic, biochemical, structural, and analytical techniques to establish L-4-Cl-Kyn biosynthesis, which is initiated by the Tar14 flavin-dependent tryptophan chlorinase and its flavin reductase partner Tar15. This work revealed the first tryptophan 2,3-dioxygenase (Tar13) and kynurenine formamidase (Tar16) enzymes that are selective for chlorinated substrates. The substrate scope of Tar13, 14, and 16 was examined revealing intriguing promiscuity, thereby opening doors for the targeted engineering of these enzymes as useful biocatalysts. Biosynthesis of L-4-Chlorokynurenine, a Lipopeptide Antibiotic Non-Proteinogenic Amino Acid and Antidepressant Prodrug.,Moore BS, Luhavaya H, Sigrist R, Chekan JR, McKinnie SMK Angew Chem Int Ed Engl. 2019 Apr 8. doi: 10.1002/anie.201901571. PMID:30963655 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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