Time-resolved experiment at an XFEL to allow us to visualize, in real time, how the shape of the catalytic site of β-lactamase determines the inhibition mechanism of this enzyme by an inhibitor.

 Our work builds on possibilities unleashed by mix-and-inject serial crystallography at XFELs. We have triggered an enzymatic reaction by mixing an inhibitor with enzyme microcrystals to report, in atomic detail and at room temperature, how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam. Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection, detailing how the inhibitor approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. The article has been published in Nature Communications (