1b87
From Proteopedia
(New page: 200px<br /><applet load="1b87" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b87, resolution 2.70Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1b87.gif|left|200px]]<br /><applet load="1b87" size=" | + | [[Image:1b87.gif|left|200px]]<br /><applet load="1b87" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1b87, resolution 2.70Å" /> | caption="1b87, resolution 2.70Å" /> | ||
'''CRYSTAL STRUCTURE OF AN AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASE'''<br /> | '''CRYSTAL STRUCTURE OF AN AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The predominant mechanism of antibiotic resistance employed by | + | BACKGROUND: The predominant mechanism of antibiotic resistance employed by pathogenic bacteria against the clinically used aminoglycosides is chemical modification of the drug. The detoxification reactions are catalyzed by enzymes that promote either the phosphorylation, adenylation or acetylation of aminoglycosides. Structural studies of these aminoglycoside-modifying enzymes may assist in the development of therapeutic agents that could circumvent antibiotic resistance. In addition, such studies may shed light on the development of antibiotic resistance and the evolution of different enzyme classes. RESULTS: The crystal structure of the aminoglycoside-modifying enzyme aminoglycoside 6'-N-acetyltransferase type li (AAC(6')-li) in complex with the cofactor acetyl coenzyme A has been determined at 2.7 A resolution. The structure establishes that this acetyltransferase belongs to the GCN5-related N-acetyltransferase superfamily, which includes such enzymes as the histone acetyltransferases GCN5 and Hat1. CONCLUSIONS: Comparison of the AAC(6')-li structure with the crystal structures of two other members of this superfamily, Serratia marcescens aminoglycoside 3-N-acetyltransferase and yeast histone acetyltransferase Hat1, reveals that of the 84 residues that are structurally similar, only three are conserved and none can be implicated as catalytic residues. Despite the negligible sequence identity, functional studies show that AAC(6')-li possesses protein acetylation activity. Thus, AAC(6')-li is both a structural and functional homolog of the GCN5-related histone acetyltransferases. |
==About this Structure== | ==About this Structure== | ||
| - | 1B87 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium] with ACO as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1B87 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium] with <scene name='pdbligand=ACO:'>ACO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B87 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Enterococcus faecium]] | [[Category: Enterococcus faecium]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Berghuis, A | + | [[Category: Berghuis, A M.]] |
| - | [[Category: Wybenga-Groot, L | + | [[Category: Wybenga-Groot, L E.]] |
[[Category: ACO]] | [[Category: ACO]] | ||
[[Category: acetyl coenzyme a]] | [[Category: acetyl coenzyme a]] | ||
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[[Category: antibiotic resistance]] | [[Category: antibiotic resistance]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:52:30 2008'' |
Revision as of 09:52, 21 February 2008
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CRYSTAL STRUCTURE OF AN AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASE
Overview
BACKGROUND: The predominant mechanism of antibiotic resistance employed by pathogenic bacteria against the clinically used aminoglycosides is chemical modification of the drug. The detoxification reactions are catalyzed by enzymes that promote either the phosphorylation, adenylation or acetylation of aminoglycosides. Structural studies of these aminoglycoside-modifying enzymes may assist in the development of therapeutic agents that could circumvent antibiotic resistance. In addition, such studies may shed light on the development of antibiotic resistance and the evolution of different enzyme classes. RESULTS: The crystal structure of the aminoglycoside-modifying enzyme aminoglycoside 6'-N-acetyltransferase type li (AAC(6')-li) in complex with the cofactor acetyl coenzyme A has been determined at 2.7 A resolution. The structure establishes that this acetyltransferase belongs to the GCN5-related N-acetyltransferase superfamily, which includes such enzymes as the histone acetyltransferases GCN5 and Hat1. CONCLUSIONS: Comparison of the AAC(6')-li structure with the crystal structures of two other members of this superfamily, Serratia marcescens aminoglycoside 3-N-acetyltransferase and yeast histone acetyltransferase Hat1, reveals that of the 84 residues that are structurally similar, only three are conserved and none can be implicated as catalytic residues. Despite the negligible sequence identity, functional studies show that AAC(6')-li possesses protein acetylation activity. Thus, AAC(6')-li is both a structural and functional homolog of the GCN5-related histone acetyltransferases.
About this Structure
1B87 is a Single protein structure of sequence from Enterococcus faecium with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of an aminoglycoside 6'-N-acetyltransferase: defining the GCN5-related N-acetyltransferase superfamily fold., Wybenga-Groot LE, Draker K, Wright GD, Berghuis AM, Structure. 1999 May;7(5):497-507. PMID:10378269
Page seeded by OCA on Thu Feb 21 11:52:30 2008
