76379-00-5Relevant articles and documents
Activation for catalysis of penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus by bacterial cell wall
Fuda, Cosimo,Hesek, Dusan,Lee, Mijoon,Morio, Ken-Ichiro,Nowak, Thomas,Mobashery, Shahriar
, p. 2056 - 2057 (2007/10/03)
Methicillin-resistant Staphylococcus aureus (MRSA) has acquired a unique penicillin-binding protein (PBP), PBP 2a, which has rendered the organism resistant to the action of all available β-lactam antibiotics. The X-ray structure of PBP 2a shows the active site in a closed conformation, consistent with resistance to inhibition by β-lactam antibiotics. However, it is known that PBP 2a avidly cross-links the S. aureus cell wall, which is its physiological function. It is shown herein that synthetic fragments of the bacterial cell wall bind in a saturable manner to PBP 2a and cause a conformational change in the protein that makes the active site more accessible to binding to a β-lactam antibiotic. These observations and measurements point to a novel strategy by nature to keep the active site of PBP 2a sheltered from the inhibitory activity of the antibiotics, yet it becomes available to the polymeric cell wall by a requisite conformational change for the critical cell wall cross-linking reaction. Copyright
Synthesis of muramyl dipeptide analogs with enhanced adjuvant activity
Kobayashi,Fukuda,Yukimasa,et al.
, p. 2570 - 2577 (2007/10/02)
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