6clx

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<StructureSection load='6clx' size='340' side='right'caption='[[6clx]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
<StructureSection load='6clx' size='340' side='right'caption='[[6clx]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6clx]] 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=6CLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CLX FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6clx]] 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=6CLX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6CLX FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tnmH, AMK26_31990 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1703937 Streptomyces sp. CB03234])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tnmH, AMK26_31990 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1703937 Streptomyces sp. CB03234])</td></tr>
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<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=6clx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6clx OCA], [http://pdbe.org/6clx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6clx RCSB], [http://www.ebi.ac.uk/pdbsum/6clx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6clx ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6clx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6clx OCA], [http://pdbe.org/6clx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6clx RCSB], [http://www.ebi.ac.uk/pdbsum/6clx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6clx ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The enediynes are among the most cytotoxic molecules known, and their use as anticancer drugs has been successfully demonstrated by targeted delivery. Clinical advancement of the anthraquinone-fused enediynes has been hindered by their low titers and lack of functional groups to enable the preparation of antibody-drug conjugates (ADCs). Here we report biochemical and structural characterization of TnmH from the tiancimycin (TNM) biosynthetic pathway, revealing that (i) TnmH catalyzes regiospecific methylation at the C-7 hydroxyl group, (ii) TnmH exhibits broad substrate promiscuity toward hydroxyanthraquinones and S-alkylated SAM analogues and catalyzes efficient installation of reactive alkyl handles, (iii) the X-ray crystal structure of TnmH provides the molecular basis to account for its broad substrate promiscuity, and (iv) TnmH as a biocatalyst enables the development of novel conjugation strategies to prepare antibody-TNM conjugates. These findings should greatly facilitate the construction and evaluation of antibody-TNM conjugates as next-generation ADCs for targeted chemotherapy.
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Characterization of TnmH as an O-Methyltransferase Revealing Insights into Tiancimycin Biosynthesis and Enabling a Biocatalytic Strategy To Prepare Antibody-Tiancimycin Conjugates.,Adhikari A, Teijaro CN, Yan X, Chang CY, Gui C, Liu YC, Crnovcic I, Yang D, Annaval T, Rader C, Shen B J Med Chem. 2020 Aug 13;63(15):8432-8441. doi: 10.1021/acs.jmedchem.0c00799. Epub, 2020 Jul 24. PMID:32658465<ref>PMID:32658465</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6clx" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 10:01, 16 September 2020

Crystal structure of TnmH in complex with SAM

PDB ID 6clx

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