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PDBsum entry 1b87
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of an aminoglycoside 6'-N-Acetyltransferase: defining the gcn5-Related n-Acetyltransferase superfamily fold.
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Authors
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L.E.Wybenga-Groot,
K.Draker,
G.D.Wright,
A.M.Berghuis.
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Ref.
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Structure, 1999,
7,
497-507.
[DOI no: ]
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PubMed id
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Abstract
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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.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1999,
7,
497-507)
copyright 1999.
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