5umy | pdb_00005umy

Crystal structure of TnmS3 in complex with tiancimycin

spinqualitylabelsall models 5umy, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5umy is a 2 chain structure with sequence from Streptomyces sp. CB03234. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.78Å Ligands: TNN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A125SA29_9ACTN Publication Abstract from PubMed The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar beta barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance. Resistance to Enediyne Antitumor Antibiotics by Sequestration.,Chang CY, Yan X, Crnovcic I, Annaval T, Chang C, Nocek B, Rudolf JD, Yang D, Hindra, Babnigg G, Joachimiak A, Phillips GN Jr, Shen B Cell Chem Biol. 2018 May 29. pii: S2451-9456(18)30183-1. doi:, 10.1016/j.chembiol.2018.05.012. PMID:29937405 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures Glyoxalase 3D structures

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