2w82

Publication Abstract from PubMed

The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alpha-beta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems.

Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance.,McMahon SA, Roberts GA, Johnson KA, Cooper LP, Liu H, White JH, Carter LG, Sanghvi B, Oke M, Walkinshaw MD, Blakely GW, Naismith JH, Dryden DT Nucleic Acids Res. 2009 Aug;37(15):4887-97. Epub 2009 Jun 8. PMID:19506028^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.