1TW2

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

1TW2 の概要

• エントリーDOI: 10.2210/pdb1tw2/pdb
• 関連するPDBエントリー: 1QZZ 1R00 1TW3
• 分子名称: Carminomycin 4-O-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 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, ... (4 entities in total)
• 機能のキーワード: anthracycline, methyltransferase, methylate, streptomyces, tailoring enzyme, polyketide, s-adenosyl-l-homocystein, structural proteomics in europe, spine, structural genomics, transferase
• 由来する生物種: Streptomyces peucetius
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80248.64

構造登録者

Jansson, A.,Koskiniemi, H.,Mantsala, P.,Niemi, J.,Schneider, G.,Structural Proteomics in Europe (SPINE) (登録日: 2004-06-30, 公開日: 2004-09-14, 最終更新日: 2024-04-03)

主引用文献

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., 279:41149-41156, 2004

PubMed Abstract: 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.

PubMed: 15273252
DOI: 10.1074/jbc.M407081200

実験手法

X-RAY DIFFRACTION (2.5 Å)