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| | <StructureSection load='5umx' size='340' side='right'caption='[[5umx]], [[Resolution|resolution]] 1.59Å' scene=''> | | <StructureSection load='5umx' size='340' side='right'caption='[[5umx]], [[Resolution|resolution]] 1.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5umx]] 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=5UMX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UMX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5umx]] is a 2 chain structure with sequence from [https://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=5UMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UMX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBF:RIBOFLAVIN'>RBF</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBF:RIBOFLAVIN'>RBF</scene></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=5umx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5umx OCA], [http://pdbe.org/5umx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5umx RCSB], [http://www.ebi.ac.uk/pdbsum/5umx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5umx ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5umx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5umx OCA], [https://pdbe.org/5umx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5umx RCSB], [https://www.ebi.ac.uk/pdbsum/5umx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5umx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A125SA29_9ACTN A0A125SA29_9ACTN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Streptomyces sp. cb03234]] | + | [[Category: Streptomyces sp. CB03234]] |
| - | [[Category: Chang, C]] | + | [[Category: Chang C]] |
| - | [[Category: Chang, C Y]] | + | [[Category: Chang CY]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Nocek B]] |
| - | [[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]
| + | [[Category: Phillips Jr GN]] |
| - | [[Category: Nocek, B]] | + | [[Category: Rudolf JD]] |
| - | [[Category: Phillips, G N]] | + | [[Category: Shen B]] |
| - | [[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-biology]]
| + | |
| - | [[Category: Tiancimycin-binding protein]]
| + | |
| Structural highlights
Function
A0A125SA29_9ACTN
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Resistance to Enediyne Antitumor Antibiotics by Sequestration. Cell Chem Biol. 2018 May 29. pii: S2451-9456(18)30183-1. doi:, 10.1016/j.chembiol.2018.05.012. PMID:29937405 doi:http://dx.doi.org/10.1016/j.chembiol.2018.05.012
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