1x7p
From Proteopedia
(New page: 200px<br /><applet load="1x7p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x7p, resolution 2.55Å" /> '''Crystal structure of...) |
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| - | [[Image:1x7p.gif|left|200px]]<br /><applet load="1x7p" size=" | + | [[Image:1x7p.gif|left|200px]]<br /><applet load="1x7p" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1x7p, resolution 2.55Å" /> | caption="1x7p, resolution 2.55Å" /> | ||
'''Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes in complex with the cofactor AdoMet'''<br /> | '''Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes in complex with the cofactor AdoMet'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The emergence of antibiotic-resistant bacterial strains is a widespread | + | The emergence of antibiotic-resistant bacterial strains is a widespread problem in medical practice and drug design, and each case requires the elucidation of the underlying mechanism. AviRb from Streptomyces viridochromogenes methylates the 2'-O atom of U2479 of the 23S ribosomal RNA in Gram-positive bacteria and thus mediates resistance to the oligosaccharide (orthosomycin) antibiotic avilamycin. The structure of AviRb with and without bound cofactor S-adenosyl-L-methionine (AdoMet) was determined, showing that it is a homodimer belonging to the SpoU family within the SPOUT class of methyltransferases. The relationships within this class were analyzed in detail and, in addition, a novel fourth SpoU sequence fingerprint is proposed. Each subunit of AviRb consists of two domains. The N-terminal domain, being related to the ribosomal proteins L30 and L7Ae, is likely to bind RNA. The C-terminal domain is related to all SPOUT methyltransferases, and is responsible for AdoMet-binding, catalysis and dimerization. The cofactor binds at the characteristic knot of the polypeptide in an unusually bent conformation. The transferred methyl group points to a broad cleft formed with the L30-type domain of the other subunit. Measurements of mutant activity revealed four important residues responsible for catalysis and allowed the modeling of a complex between AviRb and the RNA target. The model includes a specificity pocket for uracil but does not contain a base for deprotonating the 2'-O atom of U2479 on methylation. |
==About this Structure== | ==About this Structure== | ||
| - | 1X7P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_viridochromogenes Streptomyces viridochromogenes] with SAM as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1X7P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_viridochromogenes Streptomyces viridochromogenes] with <scene name='pdbligand=SAM:'>SAM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X7P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Streptomyces viridochromogenes]] | [[Category: Streptomyces viridochromogenes]] | ||
[[Category: Bechthold, A.]] | [[Category: Bechthold, A.]] | ||
| - | [[Category: Mosbacher, T | + | [[Category: Mosbacher, T G.]] |
| - | [[Category: Schulz, G | + | [[Category: Schulz, G E.]] |
[[Category: SAM]] | [[Category: SAM]] | ||
[[Category: bound cofactor adomet]] | [[Category: bound cofactor adomet]] | ||
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[[Category: spou]] | [[Category: spou]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:51:51 2008'' |
Revision as of 13:51, 21 February 2008
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Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes in complex with the cofactor AdoMet
Overview
The emergence of antibiotic-resistant bacterial strains is a widespread problem in medical practice and drug design, and each case requires the elucidation of the underlying mechanism. AviRb from Streptomyces viridochromogenes methylates the 2'-O atom of U2479 of the 23S ribosomal RNA in Gram-positive bacteria and thus mediates resistance to the oligosaccharide (orthosomycin) antibiotic avilamycin. The structure of AviRb with and without bound cofactor S-adenosyl-L-methionine (AdoMet) was determined, showing that it is a homodimer belonging to the SpoU family within the SPOUT class of methyltransferases. The relationships within this class were analyzed in detail and, in addition, a novel fourth SpoU sequence fingerprint is proposed. Each subunit of AviRb consists of two domains. The N-terminal domain, being related to the ribosomal proteins L30 and L7Ae, is likely to bind RNA. The C-terminal domain is related to all SPOUT methyltransferases, and is responsible for AdoMet-binding, catalysis and dimerization. The cofactor binds at the characteristic knot of the polypeptide in an unusually bent conformation. The transferred methyl group points to a broad cleft formed with the L30-type domain of the other subunit. Measurements of mutant activity revealed four important residues responsible for catalysis and allowed the modeling of a complex between AviRb and the RNA target. The model includes a specificity pocket for uracil but does not contain a base for deprotonating the 2'-O atom of U2479 on methylation.
About this Structure
1X7P is a Single protein structure of sequence from Streptomyces viridochromogenes with as ligand. Full crystallographic information is available from OCA.
Reference
Structure and function of the antibiotic resistance-mediating methyltransferase AviRb from Streptomyces viridochromogenes., Mosbacher TG, Bechthold A, Schulz GE, J Mol Biol. 2005 Jan 21;345(3):535-45. PMID:15581897
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