View source for 5ump


==Crystal structure of TnmS3, an antibiotic binding protein from Streptomyces sp. CB03234==
<StructureSection load='5ump' size='340' side='right'caption='[[5ump]], [[Resolution|resolution]] 1.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ump]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_sp._cb03234 Streptomyces sp. cb03234]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UMP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UMP FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tnmS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1703937 Streptomyces sp. CB03234])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ump FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ump OCA], [http://pdbe.org/5ump PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ump RCSB], [http://www.ebi.ac.uk/pdbsum/5ump PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ump ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar beta barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance.

Resistance to Enediyne Antitumor Antibiotics by Sequestration.,Chang CY, Yan X, Crnovcic I, Annaval T, Chang C, Nocek B, Rudolf JD, Yang D, Hindra, Babnigg G, Joachimiak A, Phillips GN Jr, Shen B Cell Chem Biol. 2018 May 29. pii: S2451-9456(18)30183-1. doi:, 10.1016/j.chembiol.2018.05.012. PMID:29937405<ref>PMID:29937405</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
*[[Glyoxalase 3D structures|Glyoxalase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. cb03234]]
[[Category: Chang, C]]
[[Category: Chang, C Y]]
[[Category: Joachimiak, A]]
[[Category: Structural genomic]]
[[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]
[[Category: Nocek, B]]
[[Category: Phillips, G N]]
[[Category: Rudolf, J D]]
[[Category: Shen, B]]
[[Category: Enzyme discovery for natural product biosynthesis]]
[[Category: Glyoxalase/bleomycin resistance protein/dioxygenase superfamily]]
[[Category: Mcsg]]
[[Category: Natpro]]
[[Category: PSI, Protein structure initiative]]
[[Category: Tiancimycin-binding protein]]