Dataset Information

Structural analysis of a putative aminoglycoside N-acetyltransferase from Bacillus anthracis.

ABSTRACT: For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax lethal factor and may have potential application as antitoxins. Here, we present a structural analysis of the BA2930 protein, a putative aminoglycoside acetyltransferase, which may be a component of the bacterium's aminoglycoside resistance mechanism. The determined structures revealed details of a fold characteristic only for one other protein structure in the Protein Data Bank, namely, YokD from Bacillus subtilis. Both BA2930 and YokD are members of the Antibiotic_NAT superfamily (PF02522). Sequential and structural analyses showed that residues conserved throughout the Antibiotic_NAT superfamily are responsible for the binding of the cofactor acetyl coenzyme A. The interaction of BA2930 with cofactors was characterized by both crystallographic and binding studies.

SUBMITTER: Klimecka MM

PROVIDER: S-EPMC3131501 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structural analysis of a putative aminoglycoside N-acetyltransferase from Bacillus anthracis.

Klimecka Maria M MM Chruszcz Maksymilian M Font Jose J Skarina Tatiana T Shumilin Igor I Onopryienko Olena O Porebski Przemyslaw J PJ Cymborowski Marcin M Zimmerman Matthew D MD Hasseman Jeremy J Glomski Ian J IJ Lebioda Lukasz L Savchenko Alexei A Edwards Aled A Minor Wladek W

Journal of molecular biology 20110513 3

For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax ...[more]

PMID: 21601576

Similar Datasets

Project description:BACKGROUND AND PURPOSE:The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play an important role in the detoxification and/or bioactivation of arylamine drugs and xenobiotics. In bacteria, NATs may contribute to the resistance against antibiotics such as isoniazid or sulfamides through their acetylation, which makes this enzyme family a possible drug target. Bacillus anthracis, a bacterial species of clinical significance, expresses three NAT isozymes with distinct structural and enzymatic properties, including an inactive isozyme ((BACAN)NAT3). (BACAN)NAT3 features both a non-canonical Glu residue in its catalytic triad and a truncated C-terminus domain. However, the role these unusual characteristics play in the lack of activity of the (BACAN)NAT3 isozyme remains unclear. EXPERIMENTAL APPROACH:Protein engineering, recombinant expression, enzymatic analyses with aromatic amine substrates and phylogenetic analysis approaches were conducted. KEY RESULTS:The deletion of guanine 580 (G580) in the nat3 gene was shown to be responsible for the expression of a truncated (BACAN)NAT3 isozyme. Artificial re-introduction of G580 in the nat3 gene led to a functional enzyme able to acetylate several arylamine drugs displaying structural characteristics comparable with its functional Bacillus cereus homologue ((BACCR)NAT3). Phylogenetic analysis of the nat3 gene in the B. cereus group further indicated that nat3 may constitute a pseudogene of the B. anthracis species. CONCLUSION AND IMPLICATIONS:The existence of NATs with distinct properties and evolution in Bacillus species may account for their adaptation to their diverse chemical environments. A better understanding of these isozymes is of importance for their possible use as drug targets. LINKED ARTICLES:This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.

Dataset Information

Structural analysis of a putative aminoglycoside N-acetyltransferase from Bacillus anthracis.

Publications

Structural analysis of a putative aminoglycoside N-acetyltransferase from Bacillus anthracis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets