4IAG

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

4IAG の概要

• エントリーDOI: 10.2210/pdb4iag/pdb
• 分子名称: Zbm binding protein, 1,2-ETHANEDIOL, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: structural genomics, psi-biology, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, blma_like, zorbamycin, reductive isopropylation, zorbamycin binding protein
• 由来する生物種: Streptomyces flavoviridis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15604.01

構造登録者

Cuff, M.E.,Bigelow, L.,Bruno, C.J.P.,Clancy, S.,Babnigg, G.,Bingman, C.A.,Yennamalli, R.,Lohman, J.,Ma, M.,Shen, B.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (登録日: 2012-12-06, 公開日: 2013-02-20, 最終更新日: 2017-11-15)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)