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PDBsum entry 1s60
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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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A bacterial acetyltransferase capable of regioselective n-Acetylation of antibiotics and histones.
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Authors
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M.W.Vetting,
S.Magnet,
E.Nieves,
S.L.Roderick,
J.S.Blanchard.
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Ref.
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Chem Biol, 2004,
11,
565-573.
[DOI no: ]
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PubMed id
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Abstract
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The Salmonella enterica chromosomally encoded AAC(6')-Iy has been shown to
confer broad aminoglycoside resistance in strains in which the structural gene
is expressed. The three-dimensional structures reported place the enzyme in the
large Gcn5-related N-acetyltransferase (GNAT) superfamily. The structure of the
CoA-ribostamycin ternary complex allows us to propose a chemical mechanism for
the reaction, and comparison with the Mycobacterium tuberculosis
AAC(2')-CoA-ribostamycin complex allows us to define how regioselectivity of
acetylation is achieved. The AAC(6')-Iy dimer is most structurally similar to
the Saccharomyces cerevisiae Hpa2-encoded histone acetyltransferase. We
demonstrate that AAC(6')-Iy catalyzes both acetyl-CoA-dependent
self-alpha-N-acetylation and acetylation of eukaryotic histone proteins and the
human histone H3 N-terminal peptide. These structural and catalytic similarities
lead us to propose that chromosomally encoded bacterial acetyltransferases,
including those functionally identified as aminoglycoside acetyltransferases,
are the evolutionary progenitors of the eukaryotic histone acetyltransferases.
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Figure 1.
Figure 1. Schematic of the Genomic Environment and a
Typical Acetyltransferase Reaction of AAC(6′)-Iy(A) The
genomic environment of the aminoglycoside-sensitive S. enterica
BM4361 and aminoglycoside-resistant S. enterica BM4362. A 60
kilobase pair chromosomal deletion results in the constitutive
nmpC promoter (black circle) being placed  vert,
similar 2.2 kilobases upstream of the aac(6′)-Iy-encoded
aminoglycoside acetyltransferase (red arrow).(B) Ribostamycin
acetylation catalyzed by aminoglycoside 6′-N-acetyltransferase.
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Figure 2.
Figure 2. Overall Fold of AAC(6′)-Iy(A) The
crystallographically determined structure of the S. enterica
AAC(6′)-Iy monomer. The coloring conforms to the
amino-terminal residues (β1, α1, α2, green), the central β
strands (β2–4, yellow), the central α helix and β strand
(α3, β5, red), and the carboxy-terminal region (α4, β6,
blue). CoenzymeA and ribostamycin are colored by atom type. This
coloring scheme is used throughout.(B) The S. enterica
AAC(6′)-Iy dimer showing the position of bound CoA and
ribostamycin (stick representation, colored by atom type). The
exchange of the β6 and β6′ strands is noted.(C) The
interaction between two S. enterica AAC(6′)-Iy dimers showing
the N terminally extended peptide, colored by atom type,
interacting with an adjacent dimer.(D) Closeup of the
interaction between the crystallographically observable N
terminally extended peptide and the active site channel. The
dimer is presented in surface representation with each monomer
colored in silver or bronze.
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The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2004,
11,
565-573)
copyright 2004.
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Secondary reference #1
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Title
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Kinetic and mutagenic characterization of the chromosomally encoded salmonella enterica aac(6')-Iy aminoglycoside n-Acetyltransferase.
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Authors
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S.Magnet,
T.Lambert,
P.Courvalin,
J.S.Blanchard.
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Ref.
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Biochemistry, 2001,
40,
3700-3709.
[DOI no: ]
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PubMed id
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