8gyi

Crystal structure of Fic25 (holo form) from Streptomyces ficellus

spinqualitylabelsall models 8gyi, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gyi is a 2 chain structure with sequence from Streptomyces ficellus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, IMD, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1W5T2G9_9ACTN Publication Abstract from PubMed (2,6)-Diamino-(5,7)-dihydroxyheptanoic acid (DADH), a non-proteinogenic amino acid, is converted to 1-azabicyclo[3.1.0]hexane ring-containing amino acids that are subsequently incorporated into ficellomycin and vazabitide A. The present study revealed that the sugar aminotransferase-like enzymes Fic25 and Vzb9, with a high amino acid sequence identity (56%) to each other, synthesized stereoisomers of DADH with (6S) and (6R) configurations, respectively. The crystal structure of the Fic25 complex with a PLP-(6S)-N(2)-acetyl-DADH adduct indicated that Asn45 and Gln197 (Asn205 and Ala53 in Vzb9) were located at positions that affected the stereochemistry of DADH being synthesized. A modeling study suggested that amino acid substitutions between Fic25 and Vzb9 allowed the enzymes to bind to the substrate with almost 180 degrees rotation in the C5-C7 portions of the DADH molecules, accompanied by a concomitant shift in their C1-C4 portions. In support of this result, the replacement of two corresponding residues in Fic25 and Vzb9 increased (6R) and (6S) stereoselectivities, respectively. The different stereochemistry at C6 of DADH resulted in a different stereochemistry/orientation of the aziridine portion of the 1-azabicyclo[3.1.0]hexane ring, which plays a crucial role in biological activity, between ficellomycin and vazabitide A. A phylogenic analysis suggested that Fic25 and Vzb9 evolved from sugar aminotransferases to produce unusual building blocks for expanding the structural diversity of secondary metabolites. Mechanisms of Sugar Aminotransferase-like Enzymes to Synthesize Stereoisomers of Non-proteinogenic Amino Acids in Natural Product Biosynthesis.,Kurosawa S, Okamura H, Yoshida A, Tomita T, Sone Y, Hasebe F, Shinada T, Takikawa H, Kosono S, Nishiyama M ACS Chem Biol. 2023 Feb 17;18(2):385-395. doi: 10.1021/acschembio.2c00823. Epub , 2023 Jan 20. PMID:36669120 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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