8er0

X-ray crystal structure of Tet(X6) bound to anhydrotetracycline

spinqualitylabelsall models 8er0, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8er0 is a 2 chain structure with sequence from Chryseobacterium oncorhynchi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: FAD, TDC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A316WTJ0_9FLAO An FAD-requiring monooxygenase active on some tetracycline antibiotic derivatives, which leads to their inactivation. Hydroxylates carbon 11a of tetracycline and some analogs.[HAMAP-Rule:MF_00845] Publication Abstract from PubMed Inactivation of tetracycline antibiotics by tetracycline destructases (TDases) remains a clinical and agricultural threat. TDases can be classified as type 1 Tet(X)-like TDases and type 2 soil-derived TDases. Type 1 TDases are widely identified in clinical pathogens. A combination therapy of tetracycline and a TDase inhibitor is much needed to rescue the clinical efficacy of tetracyclines. Anhydrotetracycline is a pan-TDase inhibitor that inhibits both type 1 and type 2 TDases. Here, we present structural, biochemical, and phenotypic evidence that anhydrotetracycline binds in a substrate-like orientation and competitively inhibits the type 1 TDase Tet(X6) to rescue tetracycline antibiotic activity as a sacrificial substrate. Anhydrotetracycline interacting residues of Tet(X6) are conserved within type 1 TDases, indicating a conserved binding mode and mechanism of inhibition. This mode of binding and inhibition is distinct from anhydrotetracycline's inhibition of type 2 TDases. This study forms the framework for development of next-generation therapies to counteract enzymatic tetracycline resistance. Structure of anhydrotetracycline-bound Tet(X6) reveals the mechanism for inhibition of type 1 tetracycline destructases.,Kumar H, Williford EE, Blake KS, Virgin-Downey B, Dantas G, Wencewicz TA, Tolia NH Commun Biol. 2023 Apr 17;6(1):423. doi: 10.1038/s42003-023-04792-4. PMID:37062778 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monooxygenase 3D structures

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