7f0f

Crystal structure of capreomycin phosphotransferase in complex with CMN IIB

spinqualitylabelsall models 7f0f, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7f0f is a 2 chain structure with sequence from Saccharothrix mutabilis subsp. capreolus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: DPP, KBE, MYN, UAL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q53826_STRMP Publication Abstract from PubMed Capreomycin (CMN) is an important second-line antituberculosis antibiotic isolated from Saccharothrix mutabilis subspecies capreolus. The gene cluster for CMN biosynthesis has been identified and sequenced, wherein the cph gene was annotated as a phosphotransferase likely engaging in self-resistance. Previous studies reported that Cph inactivates two CMNs, CMN IA and IIA, by phosphorylation. We, herein, report that (1) Escherichia coli harboring the cph gene becomes resistant to both CMN IIA and IIB, (2) phylogenetic analysis regroups Cph to a new clade in the phosphotransferase protein family, (3) Cph shares a three-dimensional structure akin to the aminoglycoside phosphotransferases with a high binding affinity (KD) to both CMN IIA and IIB at micromolar levels, and (4) Cph utilizes either ATP or GTP as a phosphate group donor transferring its gamma-phosphate to the hydroxyl group of CMN IIA. Until now, Cph and Vph (viomycin phosphotransferase) are the only two known enzymes inactivating peptide-based antibiotics through phosphorylation. Our biochemical characterization and structural determination conclude that Cph confers the gene-carrying species resistance to CMN by means of either chemical modification or physical sequestration, a naturally manifested belt and braces strategy. These findings add a new chapter into the self-resistance of bioactive natural products, which is often overlooked while designing new bioactive molecules. Dual-Mechanism Confers Self-Resistance to the Antituberculosis Antibiotic Capreomycin.,Pan YC, Wang YL, Toh SI, Hsu NS, Lin KH, Xu Z, Huang SC, Wu TK, Li TL, Chang CY ACS Chem Biol. 2022 Jan 21;17(1):138-146. doi: 10.1021/acschembio.1c00799. Epub, 2022 Jan 7. PMID:34994196 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase 3D structures

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