1tw3

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(New page: 200px<br /><applet load="1tw3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tw3, resolution 2.35&Aring;" /> '''Crystal structure of...)
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[[Image:1tw3.gif|left|200px]]<br /><applet load="1tw3" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1tw3, resolution 2.35&Aring;" />
 
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'''Crystal structure of Carminomycin-4-O-methyltransferase (DnrK) in complex with S-adenosyl-L-homocystein (SAH) and 4-methoxy-e-rhodomycin T (M-ET)'''<br />
 
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==Overview==
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==Crystal structure of Carminomycin-4-O-methyltransferase (DnrK) in complex with S-adenosyl-L-homocystein (SAH) and 4-methoxy-e-rhodomycin T (M-ET)==
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One of the final steps in the biosynthesis of the widely used anti-tumor, drug daunorubicin in Streptomyces peucetius is the methylation of the, 4-hydroxyl group of the tetracyclic ring system. This reaction is, catalyzed by the S-adenosyl-L-methionine-dependent carminomycin, 4-O-methyltransferase DnrK. The crystal structure of the ternary complex, of this enzyme with the bound products S-adenosyl-L-homocysteine and, 4-methoxy-epsilon-rhodomycin T has been determined to a 2.35-angstroms, resolution. DnrK is a homodimer, and the subunit displays the typical fold, of small molecule O-methyltransferases. The structure provides insights, into the recognition of the anthracycline substrate and also suggests, conformational changes as part of the catalytic cycle of the enzyme. The, position and orientation of the bound ligands are consistent with an SN2, mechanism of methyl transfer. Mutagenesis experiments on a putative, catalytic base confirm that DnrK most likely acts as an entropic enzyme in, that rate enhancement is mainly due to orientational and proximity, effects. This contrasts the mechanism of DnrK with that of other, O-methyltransferases where acid/base catalysis has been demonstrated to be, an essential contribution to rate enhancement.
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<StructureSection load='1tw3' size='340' side='right'caption='[[1tw3]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1tw3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_peucetius Streptomyces peucetius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TW3 FirstGlance]. <br>
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1TW3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_peucetius Streptomyces peucetius] with SAH and ERT as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TW3 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ERT:METHYL+(4R)-2-ETHYL-2,5,12-TRIHYDROXY-7-METHOXY-6,11-DIOXO-4-{[2,3,6-TRIDEOXY-3-(DIMETHYLAMINO)-BETA-D-RIBO-HEXOPYRANOSYL]OXY}-1H,2H,3H,4H,6H,11H-TETRACENE-1-CARBOXYLATE'>ERT</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
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==Reference==
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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=1tw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tw3 OCA], [https://pdbe.org/1tw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tw3 RCSB], [https://www.ebi.ac.uk/pdbsum/1tw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tw3 ProSAT]</span></td></tr>
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Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products., Jansson A, Koskiniemi H, Mantsala P, Niemi J, Schneider G, J Biol Chem. 2004 Sep 24;279(39):41149-56. Epub 2004 Jul 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15273252 15273252]
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</table>
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[[Category: Single protein]]
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== Function ==
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[https://www.uniprot.org/uniprot/DNRK_STRPE DNRK_STRPE] Involved in the biosynthesis of the anthracyclines carminomycin and daunorubicin (daunomycin) which are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers. In vivo, catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the 4-O-position of carminomycin to form daunorubicin. In vitro, it also methylates the anthracyclines rhodomycin D (10-carbomethoxy-13-deoxycarminomycin) and 13-deoxy-carminomycin at the 4-hydroxyl position. It is quite specific with respect to the length of the carbohydrate chain at the C7 position, but it can accept substrates with bulky substituent at C10 position.<ref>PMID:15273252</ref>
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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/tw/1tw3_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=1tw3 ConSurf].
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<div style="clear:both"></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: Streptomyces peucetius]]
[[Category: Streptomyces peucetius]]
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[[Category: Jansson, A.]]
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[[Category: Jansson A]]
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[[Category: Koskiniemi, H.]]
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[[Category: Koskiniemi H]]
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[[Category: Mantsala, P.]]
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[[Category: Mantsala P]]
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[[Category: Niemi, J.]]
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[[Category: Niemi J]]
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[[Category: Schneider, G.]]
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[[Category: Schneider G]]
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[[Category: ERT]]
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[[Category: SAH]]
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[[Category: anthracycline]]
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[[Category: methylate]]
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[[Category: methyltransferase]]
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[[Category: polyketide]]
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[[Category: s-adenosyl-l-homocystein]]
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[[Category: streptomyces]]
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[[Category: tailoring enzyme]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:38:11 2007''
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Current revision

Crystal structure of Carminomycin-4-O-methyltransferase (DnrK) in complex with S-adenosyl-L-homocystein (SAH) and 4-methoxy-e-rhodomycin T (M-ET)

PDB ID 1tw3

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