Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892

Simple item page
dc.citation.firstpage6842en_US
dc.citation.issueNumber45en_US
dc.citation.journalTitleBiochemistryen_US
dc.citation.lastpage6851en_US
dc.citation.volumeNumber54en_US
dc.contributor.authorRudolf, Jeffrey D.en_US
dc.contributor.authorBigelow, Lanceen_US
dc.contributor.authorChang, Changsooen_US
dc.contributor.authorCuff, Marianne E.en_US
dc.contributor.authorLohman, Jeremy R.en_US
dc.contributor.authorChang, Chin-Yuanen_US
dc.contributor.authorMa, Mingen_US
dc.contributor.authorYang, Dongen_US
dc.contributor.authorClancy, Shondaen_US
dc.contributor.authorBabnigg, Gyorgyen_US
dc.contributor.authorJoachimiak, Andrzejen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorShen, Benen_US
dc.date.accessioned2017-05-12T17:10:13Zen_US
dc.date.available2017-05-12T17:10:13Zen_US
dc.date.issued2015en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationRudolf, Jeffrey D., Bigelow, Lance, Chang, Changsoo, et al.. "Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892." <i>Biochemistry,</i> 54, no. 45 (2015) American Chemical Society: 6842-6851. http://dx.doi.org/10.1021/acs.biochem.5b01008.en_US
dc.identifier.doihttp://dx.doi.org/10.1021/acs.biochem.5b01008en_US
dc.identifier.urihttps://hdl.handle.net/1911/94241en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.en_US
dc.titleCrystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Zorbamycin-Binding.pdf
Size:
1.43 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
BioSciences Publications
Chemistry Publications