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5umy

From Proteopedia

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Current revision

Crystal structure of TnmS3 in complex with tiancimycin

Structural highlights

5umy is a 2 chain structure with sequence from Streptomyces sp. CB03234. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.78Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5umy"

@@ Line 3: / Line 3: @@
 <StructureSection load='5umy' size='340' side='right'caption='[[5umy]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5umy]] 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=5UMY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UMY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5umy]] 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=5UMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UMY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TNN:(1aS,11S,11aR,14Z,18R)-3,8,18-trihydroxy-11a-[(1R)-1-hydroxyethyl]-7-methoxy-11,11a-dihydro-4H-11,1a-hept[3]ene[1,5]diynonaphtho[2,3-h]oxireno[c]quinoline-4,9(10H)-dione'>TNN</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]] 1.78&#8491;</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=TNN:(1aS,11S,11aR,14Z,18R)-3,8,18-trihydroxy-11a-[(1R)-1-hydroxyethyl]-7-methoxy-11,11a-dihydro-4H-11,1a-hept[3]ene[1,5]diynonaphtho[2,3-h]oxireno[c]quinoline-4,9(10H)-dione'>TNN</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=5umy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5umy OCA], [http://pdbe.org/5umy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5umy RCSB], [http://www.ebi.ac.uk/pdbsum/5umy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5umy 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=5umy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5umy OCA], [https://pdbe.org/5umy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5umy RCSB], [https://www.ebi.ac.uk/pdbsum/5umy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5umy ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A125SA29_9ACTN A0A125SA29_9ACTN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 28: @@
 </StructureSection>
 [[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: Lyase]]
-[[Category: Mcsg]]
-[[Category: Natpro]]
-[[Category: Psi-biology]]
-[[Category: Tiancimycin-binding protein]]

5umy

From Proteopedia

Current revision

Crystal structure of TnmS3 in complex with tiancimycin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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