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1tw2

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Revision as of 09:04, 21 March 2018

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

Structural highlights

1tw2 is a 2 chain structure with sequence from As 4.1799. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1qzz, 1r00, 1tw3
Gene:	dnrk (AS 4.1799)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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:15273252^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jansson A, Koskiniemi H, Mantsala P, Niemi J, Schneider G. Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products. J Biol Chem. 2004 Sep 24;279(39):41149-56. Epub 2004 Jul 24. PMID:15273252 doi:10.1074/jbc.M407081200
↑ Jansson A, Koskiniemi H, Mantsala P, Niemi J, Schneider G. Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products. J Biol Chem. 2004 Sep 24;279(39):41149-56. Epub 2004 Jul 24. PMID:15273252 doi:10.1074/jbc.M407081200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tw2"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Carminomycin-4-O-methyltransferase (DnrK) in complex with S-adenosyl-L-homocystein (SAH) and 4-methoxy-e-rhodomycin T (M-ET)==
 <StructureSection load='1tw2' size='340' side='right' caption='[[1tw2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qzz|1qzz]], [[1r00|1r00]], [[1tw3|1tw3]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dnrk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1950 AS 4.1799])</td></tr>
-<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=1tw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tw2 OCA], [http://pdbe.org/1tw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tw2 RCSB], [http://www.ebi.ac.uk/pdbsum/1tw2 PDBsum]</span></td></tr>
+<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=1tw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tw2 OCA], [http://pdbe.org/1tw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tw2 RCSB], [http://www.ebi.ac.uk/pdbsum/1tw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tw2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tw/1tw2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tw/1tw2_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1tw2

From Proteopedia

Revision as of 09:04, 21 March 2018

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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