PDBsum entry 1s60

Transferase

PDB id: 1s60

Contents

Protein chain

152 a.a. *

Ligands

SO4

COA

* Residue conservation analysis

PDB id:

1s60

Name:

Transferase

Title:

Aminoglycoside n-acetyltransferase aac(6')-iy in complex with coa and n-terminal his(6)-tag (crystal form 2)

Structure:

Aminoglycoside 6'-n-acetyltransferase. Chain: a. Synonym: aminoglycoside n-acetyltransferase aac(6')-iy. Engineered: yes

Source:

Salmonella enteritidis. Organism_taxid: 592. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

3.00Å R-factor: 0.225 R-free: 0.267

Authors:

M.W.Vetting,S.Magnet,E.Nieves,S.L.Roderick,J.S.Blanchard

Key ref:

M.W.Vetting et al. (2004). A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones. Chem Biol, 11, 565-573. PubMed id: 15123251 DOI: 10.1016/j.chembiol.2004.03.017

Date:

22-Jan-04 Release date: 18-May-04

Protein chain

Q9R381  (AAC6_SALEN) -  Aminoglycoside N(6')-acetyltransferase type 1 from Salmonella enteritidis

Seq: 145 a.a.

Struc: 152 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.82 - aminoglycoside 6'-N-acetyltransferase.
• Reaction: kanamycin B + acetyl-CoA = N(6')-acetylkanamycin B + CoA + H⁺

kanamycin B + acetyl-CoA = N(6')-acetylkanamycin B (Bound ligand (Het Group name = COA) corresponds exactly) + CoA + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.chembiol.2004.03.017

Chem Biol 11:565-573 (2004)

PubMed id: 15123251

A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones.

M.W.Vetting, S.Magnet, E.Nieves, S.L.Roderick, J.S.Blanchard.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Cell Press: Chem Biol (2004, 11, 565-573) copyright 2004.

Figures were selected by the author.