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

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell AdhesionThe 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.

Biochemistry. 2015 Nov 5. [Epub ahead of print]

ACS Publications
©2015 American Chemical Society

  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.

Another SBC Highlight:

Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2
Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

An S-adenosyl-L-homocysteine (SAH) cofactor and an inhibiting H3K27M cancer mutant peptide bound to the catalytic SET domain of Ezh2 were captured in the crystal structures of both basal and stimulated complexes.

Science. 2015 Oct 16;350(6258):aac4383.
doi: 10.1126/science.aac4383.
Epub 2015 Oct 15.

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APS requests the Experimental Safety Approval Form (ESAF) be submitted at least seven days prior to your scheduled beamtime.


Failure to submit your ESAF in advance may result in delaying the beginning of your experiment.


Future Meetings:


Biophysical Society Annual Meeting

February 27 - March 02, 2016

Los Angeles Convention Center; Los Angeles, CA


APS/CNM Users Meeting

May 09-12, 2016

Advanced Photon Source, Argonne National Laboratory; Argonne, IL


American Crystallographic Association, 2016

July 22-26, 2016

Downtown Sheraton Hotel; Denver CO


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SBC Beamtime Request System

The on-line SBC Beamtime Request System allows users to view available beamtime on 19-ID and 19-BM, and to submit a request for rapid beamtime allocation.

Beamtime is available to the research community via a peer reviewed proposal system; it is supported by the U.S. Department of Energy, Office of Biological and Environmental Research.

Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2013 2014 2015 TOTAL
PDB Depositions 238 50 258 34 115 12 4559

APS Publications Database:

Publications Total
SBC-CAT Publication List: 19-ID 1341
SBC-CAT Publication List: 19-BM 506
SBC-CAT Publication List: ALL
APS Publications Database

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Beginning August 01, 2015 the Midwest Center for Structural Genomics (MCSG) will start accepting applications for access to the MCSG User Resource.


MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.


For further information, please contact Andrzej Joachimiak.


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