4iag

Crystal structure of ZbmA, the zorbamycin binding protein from Streptomyces flavoviridis

spinqualitylabelsall models 4iag, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4iag is a 1 chain structure with sequence from Streptomyces pilosus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: EDO, GOL, ILY, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B9UIZ4_9ACTN Publication Abstract from PubMed The bleomycins (BLMs), tallysomycins (TLMs), phleomycin, and zorbamycin (ZBM) are members of the BLM family of glycopeptide-derived antitumor antibiotics. The BLM-producing Streptomyces verticillus ATCC15003 and the TLM-producing Streptoalloteichus hindustanus E465-94 ATCC31158 both possess at least two self-resistance elements, an N-acetyltransferase and a binding protein. The N-acetyltransferase provides resistance by disrupting the metal-binding domain of the antibiotic that is required for activity, while the binding protein confers resistance by sequestering the metal-bound antibiotic and preventing drug activation via molecular oxygen. We recently established that the ZBM producer, Streptomyces flavoviridis ATCC21892, lacks the N-acetyltransferase resistance gene and that the ZBM-binding protein, ZbmA, is sufficient to confer resistance in the producing strain. To investigate the resistance mechanism attributed to ZbmA, we determined the crystal structures of apo and Cu(II)-ZBM-bound ZbmA at high resolutions of 1.90 and 1.65 A, respectively. A comparison and contrast with other structurally characterized members of the BLM-binding protein family revealed key differences in the protein-ligand binding environment that fine-tunes the ability of ZbmA to sequester metal-bound ZBM and supports drug sequestration as the primary resistance mechanism in the producing organisms of the BLM family of antitumor antibiotics. Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892.,Rudolf JD, Bigelow L, Chang C, Cuff ME, Lohman JR, Chang CY, Ma M, Yang D, Clancy S, Babnigg G, Joachimiak A, Phillips GN Jr, Shen B Biochemistry. 2015 Nov 17;54(45):6842-51. doi: 10.1021/acs.biochem.5b01008. Epub , 2015 Nov 5. PMID:26512730 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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