1R00

Crystal structure of aclacinomycin-10-hydroxylase (RdmB) in complex with S-adenosyl-L-homocysteine (SAH)

Summary for 1R00

• Entry DOI: 10.2210/pdb1r00/pdb
• Related: 1QZZ
• Descriptor: aclacinomycin-10-hydroxylase, ACETATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: anthracycline, hydroxylase, methyltransferase, polyketide, streptomyces, tailoring enzyme, oxidoreductase, transferase
• Biological source: Streptomyces purpurascens
• Total number of polymer chains: 1
• Total formula weight: 40281.40

Authors

Jansson, A.,Niemi, J.,Lindqvist, Y.,Mantsala, P.,Schneider, G. (deposition date: 2003-09-19, release date: 2003-11-25, Last modification date: 2023-08-23)

Primary citation

Jansson, A.,Niemi, J.,Lindqvist, Y.,Mantsala, P.,Schneider, G.
Crystal Structure of Aclacinomycin-10-Hydroxylase, a S-Adenosyl-L-Methionine-dependent Methyltransferase Homolog Involved in Anthracycline Biosynthesis in Streptomyces purpurascens.
J.Mol.Biol., 334:269-280, 2003

PubMed Abstract: Anthracyclines are aromatic polyketide antibiotics, and several of these compounds are widely used as anti-tumor drugs in chemotherapy. Aclacinomycin-10-hydroxylase (RdmB) is one of the tailoring enzymes that modify the polyketide backbone in the biosynthesis of these metabolites. RdmB, a S-adenosyl-L-methionine-dependent methyltransferase homolog, catalyses the hydroxylation of 15-demethoxy-epsilon-rhodomycin to beta-rhodomycin, one step in rhodomycin biosynthesis in Streptomyces purpurascens. The crystal structure of RdmB, determined by multiwavelength anomalous diffraction to 2.1A resolution, reveals that the enzyme subunit has a fold similar to methyltransferases and binds S-adenosyl-L-methionine. The N-terminal domain, which consists almost exclusively of alpha-helices, is involved in dimerization. The C-terminal domain contains a typical alpha/beta nucleotide-binding fold, which binds S-adenosyl-L-methionine, and several of the residues interacting with the cofactor are conserved in O-methyltransferases. Adjacent to the S-adenosyl-L-methionine molecule there is a large cleft extending to the enzyme surface of sufficient size to bind the substrate. Analysis of the putative substrate-binding pocket suggests that there is no enzymatic group in proximity of the substrate 15-demethoxy-epsilon-rhodomycin, which could assist in proton abstraction and thus facilitate methyl transfer. The lack of a suitably positioned catalytic base might thus be one of the features responsible for the inability of the enzyme to act as a methyltransferase.

PubMed: 14607118
DOI: 10.1016/j.jmb.2003.09.061

Experimental method

X-RAY DIFFRACTION (2.5 Å)