1r00
From Proteopedia
(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 ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1r00.gif|left|200px]]<br /><applet load="1r00" size=" | + | [[Image:1r00.gif|left|200px]]<br /><applet load="1r00" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1r00, resolution 2.5Å" /> | caption="1r00, resolution 2.5Å" /> | ||
'''Crystal structure of aclacinomycin-10-hydroxylase (RdmB) in complex with S-adensyl-L-homocystein (SAH)'''<br /> | '''Crystal structure of aclacinomycin-10-hydroxylase (RdmB) in complex with S-adensyl-L-homocystein (SAH)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Anthracyclines are aromatic polyketide antibiotics, and several of these | + | 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== | ==About this Structure== | ||
| - | 1R00 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_purpurascens Streptomyces purpurascens] with ACT and SAH as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1R00 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_purpurascens Streptomyces purpurascens] with <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R00 OCA]. |
==Reference== | ==Reference== | ||
| Line 27: | Line 27: | ||
[[Category: tailoring enzyme]] | [[Category: tailoring enzyme]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:45:32 2008'' |
Revision as of 12:45, 21 February 2008
|
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 and 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
Page seeded by OCA on Thu Feb 21 14:45:32 2008
