Functional characterization of proteins requires linking structure and dynamics, but traditional X-ray crystallography provides only static snapshots. Serial time-resolved crystallography enables direct visualization of structural changes over time, including internal motions and solvent interactions. We developed fixed-target approaches such as “Hit And REturn” (HARE) and reaction initiation...
The β-lactamase enzymes degrade β-lactam antibiotics, exemplified by penicillin. As such, the families of metallo- and serine β-lactamases are responsible for a major antimicrobial resistance mechanism in many clinically relevant species of Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. To preserve the antimicrobial activity of β-lactam...
Protein dynamics are critical for function, but it remains challenging to understand, in atomic detail, how a molecule’s biological activity is enabled by the physical coupling of its conformational fluctuations across varied length and time scales. Time-dependent X-ray crystallographic measurements of molecular structure can overcome some of the limitations of traditional structural biology...
Time-resolved serial crystallography (TR-SX) is a leading technique for capturing biological processes as molecular movies on extremely fast timescales—fulfilling a long-standing goal in structural biology. The method involves delivering microcrystals into a powerful, pulsed X-ray beam to collect individual diffraction patterns from each crystal. By compiling thousands of these patterns,...
