1r00
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(New page: 200px<br /><applet load="1r00" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r00, resolution 2.5Å" /> '''Crystal structure of ...)
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Revision as of 19:45, 24 November 2007
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Crystal structure of aclacinomycin-10-hydroxylase (RdmB) in complex with S-adensyl-L-homocystein (SAH)
Overview
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.
About this Structure
1R00 is a Single protein structure of sequence from Streptomyces purpurascens with ACT and SAH as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of aclacinomycin-10-hydroxylase, a S-adenosyl-L-methionine-dependent methyltransferase homolog involved in anthracycline biosynthesis in Streptomyces purpurascens., Jansson A, Niemi J, Lindqvist Y, Mantsala P, Schneider G, J Mol Biol. 2003 Nov 21;334(2):269-80. PMID:14607118
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