1tw3
From Proteopedia
(New page: 200px<br /><applet load="1tw3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tw3, resolution 2.35Å" /> '''Crystal structure of...) |
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| - | [[Image:1tw3.gif|left|200px]]<br /><applet load="1tw3" size=" | + | [[Image:1tw3.gif|left|200px]]<br /><applet load="1tw3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1tw3, resolution 2.35Å" /> | caption="1tw3, resolution 2.35Å" /> | ||
'''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 /> | '''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 /> | ||
==Overview== | ==Overview== | ||
| - | One of the final steps in the biosynthesis of the widely used anti-tumor | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 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:// | + | 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 <scene name='pdbligand=SAH:'>SAH</scene> and <scene name='pdbligand=ERT:'>ERT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TW3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tailoring enzyme]] | [[Category: tailoring enzyme]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:03 2008'' |
Revision as of 13:18, 21 February 2008
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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)
Overview
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.
About this Structure
1TW3 is a Single protein structure of sequence from Streptomyces peucetius with and as ligands. Full crystallographic information is available from OCA.
Reference
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
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