6bbx: Difference between revisions
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==Crystal structure of TnmS3 in complex with TNM C== | |||
<StructureSection load='6bbx' size='340' side='right'caption='[[6bbx]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6bbx]] 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=6BBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BBX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D77:methyl+(2R,3R)-2,3-dihydroxy-3-[(1aS,11S,11aR,14Z,18R)-3,7,8,18-tetrahydroxy-4,9-dioxo-4,9,10,11-tetrahydro-11aH-11,1a-hept[3]ene[1,5]diynonaphtho[2,3-h]oxireno[c]quinolin-11a-yl]butanoate'>D77</scene></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=6bbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bbx OCA], [https://pdbe.org/6bbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bbx RCSB], [https://www.ebi.ac.uk/pdbsum/6bbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bbx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A125SA29_9ACTN A0A125SA29_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6bbx" style="background-color:#fffaf0;"></div> | ||
[[Category: Chang | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | ||
[[Category: | *[[Glyoxalase 3D structures|Glyoxalase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces sp. CB03234]] | |||
[[Category: Chang C]] | |||
[[Category: Chang CY]] | |||
[[Category: Joachimiak A]] | |||
[[Category: Nocek B]] | |||
[[Category: Phillips Jr GN]] | |||
[[Category: Rudolf JD]] | |||
[[Category: Shen B]] | |||
Latest revision as of 17:37, 4 October 2023
Crystal structure of TnmS3 in complex with TNM CCrystal structure of TnmS3 in complex with TNM C
Structural highlights
FunctionPublication Abstract from PubMedThe 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 AlsoReferences
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