Seeing the interaction between antibiotics and the bugs they are designed to attack in three dimensions could help combat drug-resistant bacteria.
A team from Oxford University and Dundee University recently used the Diamond Light Source and ESRF to solve the 3D structure of the penicillin binding protein PBP3 from the bacterium Pseudomonas aeruginosa.
A report of the research is published in the Journal of Molecular Biology.
P. aeruginosa poses a particular risk to burns victims or people with a compromised immune system, for instance chemotherapy patients or people with HIV, and is resistant to most common antibiotics. The flexibility of penicillin binding proteins, such as PBP3, is key to how bacteria develop a resistance to drugs, mutating these proteins so that antibiotics can no longer ‘lock on’ to their intended targets.
By creating an accurate 3D picture of how the antibiotic binds to the protein PBP3, using X-rays produced at Diamond, the team now hope that it will be possible to develop new drugs to attack and destroy this tough bacterium.
Jingshan Ren, a member of the Oxford team, told us: 'The crystal structures of PBP3 and its complexes with antibiotics reveal how these drugs attack the bacteria in atomic resolution and provide a platform for developing new antibiotics to combat resistance using structure based drug design.'
The team included researchers from Oxford's Division of Structural Biology.