View source for 4iag


==Crystal structure of ZbmA, the zorbamycin binding protein from Streptomyces flavoviridis==
<StructureSection load='4iag' size='340' side='right' caption='[[4iag]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4iag]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_flavoviridis"_preobrazhenskaya_et_al._in_gauze_et_al._1957 "actinomyces flavoviridis" preobrazhenskaya et al. in gauze et al. 1957]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IAG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ILY:N~6~-PROPAN-2-YL-L-LYSINE'>ILY</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">zbmA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=66889 "Actinomyces flavoviridis" Preobrazhenskaya et al. in Gauze et al. 1957])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iag OCA], [http://pdbe.org/4iag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iag RCSB], [http://www.ebi.ac.uk/pdbsum/4iag PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iag ProSAT]</span></td></tr>
</table>
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== 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<ref>PMID:26512730</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinomyces flavoviridis preobrazhenskaya et al. in gauze et al. 1957]]
[[Category: Babnigg, G]]
[[Category: Bigelow, L]]
[[Category: Bingman, C A]]
[[Category: Bruno, C J.P]]
[[Category: Clancy, S]]
[[Category: Cuff, M E]]
[[Category: Joachimiak, A]]
[[Category: Lohman, J]]
[[Category: Structural genomic]]
[[Category: Ma, M]]
[[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]
[[Category: Phillips, G N]]
[[Category: Shen, B]]
[[Category: Yennamalli, R]]
[[Category: Blma_like]]
[[Category: Enzyme discovery for natural product biosynthesis]]
[[Category: Mcsg]]
[[Category: Natpro]]
[[Category: Psi-biology]]
[[Category: Reductive isopropylation]]
[[Category: Zorbamycin]]
[[Category: Zorbamycin binding protein]]