Gram-positive and Gram-negative bacteria are common causes of serious diseases such as pneumonia and complicated skin infections. Resistance to currently available antibiotics is increasing and presents a vital medical need. Disturbingly, diseases caused by multidrug-resistant (MDR) Gram-positive pathogens such as MRSA (methicillin-resistant staphylococcus aureus) are becoming more commonplace, turning what were previously easily managed conditions into urgent, life-threatening problems.

As part of the response to this emerging resistance new antibacterial targets are being identified and characterised. The selection of bacterial processes that are not targeted by current antibiotics avoids potential cross-resistance. We present here the crystal structure of the 43kDa N-terminal ATPase domain of the Topoisomerase IV ParE subunit from the Gram negative pathogen Pseudomonas aeruginosa. Structures were determined to 1.8 Å resolution for the protein in complex with two different non-hydrolysable ATP analogues, allowing detailed characterisation of the ATP-binding site. The implications of the structure and its use in ongoing structure-based drug design will be discussed.