8hk0

Crystal structure of Fic32-33 complex from Streptomyces ficellus NRRL 8067

spinqualitylabelsall models 8hk0, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hk0 is a 4 chain structure with sequence from Streptomyces ficellus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.29Å Ligands: 1PE, FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1W5T2G8_9ACTN Publication Abstract from PubMed Ficellomycin, azinomycins, and vazabitide A are nonribosomal peptide natural products characterized by an amino acid unit that contains a similar 1-azabicyclo[3.1.0]hexane (ABCH) pharmacophore. This unit is derived from diamino-dihydroxy-heptanic acid (DADH); however, the process through which linear DADH is cyclized to furnish an ABCH ring system remains poorly understood. Based on the reconstitution of the route of the ABCH-containing unit by blending genes/enzymes involved in the biosynthesis of ficellomycin and azinomycins, we report that ABCH formation is completed by an oxidase heterotetramer with the association of a nonribosomal peptide synthetase (NRPS). The DADH precursor was prepared in Escherichia coli to produce a conjugate subjected to in vitro enzymatic hydrolysis for offloading from an amino-group carrier protein. To furnish an aziridine ring, DADH was processed by C7-hydroxyl sulfonation and sulfate elimination-coupled cyclization. Further cyclization leading to an azabicyclic hexane pharmacophore was proved to occur in the NRPS, where the oxidase heterotetramer functions in trans and catalyzes alpha,beta-dehydrogenation to initiate the formation of a fused five-membered nitrogen heterocycle. The identity of ABCH was validated by utilization of the resultant ABCH-containing unit in the total biosynthesis of ficellomycin. Biochemical characterization, crystal structure, and site-specific mutagenesis rationalize the catalytic mechanism of the unusual oxidase heterotetramer. Oxidase Heterotetramer Completes 1-Azabicyclo[3.1.0]hexane Formation with the Association of a Nonribosomal Peptide Synthetase.,Cheng Y, Yi X, Zhang Y, He Q, Chen D, Cao W, Fang P, Liu W J Am Chem Soc. 2023 Apr 26;145(16):8896-8907. doi: 10.1021/jacs.2c12507. Epub , 2023 Apr 12. PMID:37043819 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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