1tw3
From Proteopedia
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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 SAH and ERT 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
Page seeded by OCA on Wed Nov 21 03:38:11 2007
