2gkd

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(New page: 200px<br /><applet load="2gkd" size="350" color="white" frame="true" align="right" spinBox="true" caption="2gkd" /> '''Structural insight into self-sacrifice mecha...)
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[[Image:2gkd.gif|left|200px]]<br /><applet load="2gkd" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2gkd" />
 
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'''Structural insight into self-sacrifice mechanism of enediyne resistance'''<br />
 
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==Overview==
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==Structural insight into self-sacrifice mechanism of enediyne resistance==
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The recent discovery of the first "self-sacrifice" mechanism for bacterial, resistance to the enediyne antitumor antibiotics, where enediyne-induced, proteolysis of the resistance protein CalC inactivates both the highly, reactive metabolite and the resistance protein, revealed yet another, ingenious bacterial mechanism for controlling reactive metabolites. As, reported herein, the first 3D structures of CalC and CalC in complex with, calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute, regulatory protein (StAR)-related transfer (START) domain superfamily. In, contrast to previous studies of proteins known to bind DNA-damaging, natural products ( e.g ., bleomycins, mitomycins, and nine-membered, chromoprotein enediynes), this is the first demonstrated involvement of a, START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM, in complex with CalC is positioned for direct hydrogen abstraction from, Gly113 to initiate the oxidative proteolysis-based resistance mechanism., These structural studies also illuminate, for the first time, a small, DNA-binding region within CalC that may serve to localize CalC to the, enediyne target (DNA). Given the role of START domains in, nuclear/cytosolic transport and translocation, this structural study also, may implicate START domains as post-endocytotic intracellular chaperones, for enediyne-based therapeutics such as MyloTarg.
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<StructureSection load='2gkd' size='340' side='right'caption='[[2gkd]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gkd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Micromonospora_echinospora Micromonospora echinospora]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GKD FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gkd OCA], [https://pdbe.org/2gkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gkd RCSB], [https://www.ebi.ac.uk/pdbsum/2gkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gkd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q8KNF0_MICEC Q8KNF0_MICEC]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/2gkd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gkd ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The recent discovery of the first "self-sacrifice" mechanism for bacterial resistance to the enediyne antitumor antibiotics, where enediyne-induced proteolysis of the resistance protein CalC inactivates both the highly reactive metabolite and the resistance protein, revealed yet another ingenious bacterial mechanism for controlling reactive metabolites. As reported herein, the first 3D structures of CalC and CalC in complex with calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute regulatory protein (StAR)-related transfer (START) domain superfamily. In contrast to previous studies of proteins known to bind DNA-damaging natural products ( e.g ., bleomycins, mitomycins, and nine-membered chromoprotein enediynes), this is the first demonstrated involvement of a START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM in complex with CalC is positioned for direct hydrogen abstraction from Gly113 to initiate the oxidative proteolysis-based resistance mechanism. These structural studies also illuminate, for the first time, a small DNA-binding region within CalC that may serve to localize CalC to the enediyne target (DNA). Given the role of START domains in nuclear/cytosolic transport and translocation, this structural study also may implicate START domains as post-endocytotic intracellular chaperones for enediyne-based therapeutics such as MyloTarg.
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==About this Structure==
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Structural insight into the self-sacrifice mechanism of enediyne resistance.,Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL, Thorson JS ACS Chem Biol. 2006 Aug 22;1(7):451-60. PMID:17168523<ref>PMID:17168523</ref>
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2GKD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Micromonospora_echinospora Micromonospora echinospora]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GKD OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural insight into the self-sacrifice mechanism of enediyne resistance., Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL, Thorson JS, ACS Chem Biol. 2006 Aug 22;1(7):451-60. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17168523 17168523]
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</div>
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<div class="pdbe-citations 2gkd" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Micromonospora echinospora]]
[[Category: Micromonospora echinospora]]
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[[Category: Single protein]]
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[[Category: Singh S]]
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[[Category: Singh, S.]]
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[[Category: Thorson JS]]
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[[Category: Thorson, J.S.]]
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[[Category: start domain protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:01:48 2008''
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Structural insight into self-sacrifice mechanism of enediyne resistance

PDB ID 2gkd

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