5CJ3

Crystal structure of the zorbamycin binding protein (ZbmA) from Streptomyces flavoviridis with zorbamycin

Summary for 5CJ3

• Entry DOI: 10.2210/pdb5cj3/pdb
• Related: 4IAG
• Descriptor: Zbm binding protein, Zorbamycin, COPPER (II) ION, ... (5 entities in total)
• Functional Keywords: structural genomics, psi-biology, midwest center for structural genomics, mcsg, natpro, zorbamycin binding protein, enzyme discovery for natural product biosynthesis, zorbamycin, antibiotic binding protein-antibiotic complex, antibiotic binding protein/antibiotic
• Biological source: Streptomyces flavoviridis
• Total number of polymer chains: 2
• Total formula weight: 32784.03

Authors

Chang, C.,Bigelow, L.,Clancy, S.,Babnigg, G.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Rudolf, J.D.,Ma, M.,Chang, C.-Y.,Lohman, J.R.,Yang, D.,Shen, B.,Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2015-07-13, release date: 2015-07-22, Last modification date: 2025-10-22)

Primary citation

Rudolf, J.D.,Bigelow, L.,Chang, C.,Cuff, M.E.,Lohman, J.R.,Chang, C.Y.,Ma, M.,Yang, D.,Clancy, S.,Babnigg, G.,Joachimiak, A.,Phillips, G.N.,Shen, B.
Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892.
Biochemistry, 54:6842-6851, 2015

PubMed Abstract: 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 Å, 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.

PubMed: 26512730
DOI: 10.1021/acs.biochem.5b01008

Experimental method

X-RAY DIFFRACTION (1.6499 Å)