8zt4

Complex structure of N-acetyltransferase SbzI and carrier protein SbzG in the biosynthesis of altemicidin

spinqualitylabelsall models 8zt4, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8zt4 is a 2 chain structure with sequence from Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: 4HH, BCT, CL, SCN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A3T0ZHG5_STRSQ A0A3T0ZHH1_STRSQ Publication Abstract from PubMed The general control non-repressible 5 (GCN5)-related N-acetyltransferase (GNAT) SbzI, in the biosynthesis of the sulfonamide antibiotic altemicidin, catalyzes the transfer of the 2-sulfamoylacetyl (2-SA) moiety onto 6-azatetrahydroindane dinucleotide. While most GNAT superfamily utilize acyl-coenzyme A (acyl-CoA) as substrates, SbzI recognizes a carrier-protein (CP)-tethered 2-SA substrate. Moreover, SbzI is the only naturally occurring enzyme that catalyzes the direct incorporation of sulfonamide, a valuable pharmacophore in medicinal chemistry. Here, we present the structure-function analysis and structure-based engineering of SbzI. The crystal structure of SbzI in complex with the CP SbzG, along with cross-linking and isothermal titration calorimetry analyses of their variants, revealed the structural basis for CP recognition by the GNAT SbzI. Furthermore, docking simulation, molecular dynamics simulation, and mutagenesis studies indicated the intimate structural details of the unique reaction mechanism of SbzI, which does not utilize a general base residue in contrast to other typical GNATs. These findings facilitated rational engineering of the enzyme to expand the substrate range and to generate azaindane dinucleotide derivatives. Structure-function analysis of carrier protein-dependent 2-sulfamoylacetyl transferase in the biosynthesis of altemicidin.,Zhu Y, Mori T, Karasawa M, Shirai K, Cheng W, Terada T, Awakawa T, Abe I Nat Commun. 2024 Dec 30;15(1):10896. doi: 10.1038/s41467-024-55265-z. PMID:39738057 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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