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SUMMARY:Time-resolved macromolecular crystallography studies of AmpCEC usi
 ng synchrotron and XFEL radiation
DTSTART;VALUE=DATE-TIME:20250924T073000Z
DTEND;VALUE=DATE-TIME:20250924T074500Z
DTSTAMP;VALUE=DATE-TIME:20260524T130014Z
UID:indico-contribution-1857@lindico453.srv.lu.se
DESCRIPTION:Speakers: Emily Freeman (University of Oxford)\nThe β-lactama
 se enzymes degrade β-lactam antibiotics\, exemplified by penicillin. As s
 uch\, the families of metallo- and serine β-lactamases are responsible fo
 r a major antimicrobial resistance mechanism in many clinically relevant s
 pecies of Gram-negative bacteria\, including Escherichia coli\, Klebsiella
  pneumoniae and Pseudomonas aeruginosa. To preserve the antimicrobial acti
 vity of β-lactam antibiotics\, inhibitors of β-lactamases can be used in
  combination with a β-lactam antibiotic during treatment of an antimicrob
 ial resistant infection. However\, these inhibitors often have a narrow sp
 ectrum of activity against β-lactamases\, and other bacterial mechanisms 
 of resistance against them. To further development of novel β-lactamase i
 nhibitors\, we apply time-resolved serial femtosecond and synchrotron crys
 tallography (tr-SF/SX) techniques to investigate the acylation of the β-l
 actamase AmpC from Escherichia coli by avibactam\, a clinically approved 
 β-lactamase inhibitor. Previously\, tr-SF/SX data gathered by using a “
 drop-on-demand” sample delivery system revealed that covalent binding of
  avibactam to the AmpC active site occurred in a time frame quicker than 2
 00 ms and as such pre-acylated time-resolved structures could not be obtai
 ned using this system. In the interest of capturing earlier time points us
 ing this enzymatic system\, we have turned our focus to using a “drop-on
 -chip” fixed target sample delivery system\, addressing contamination is
 sues and implementing robust controls in our setup for accurate data colle
 ction. Currently\, we are employing a drop-on-chip fixed target sample del
 ivery system to access time points >1 ms at XFELs and >10 ms at synchrotro
 ns such as Diamond Light Source.\n\nAuthors:\nEmily Freeman\, Jos Kamps\, 
 Pierre Aller\, Christopher Schofield\, Allen Orville\n\nhttps://lindico453
 .srv.lu.se/event/583/contributions/1857/
LOCATION:LINXS at The Loop
URL:https://lindico453.srv.lu.se/event/583/contributions/1857/
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