Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography

Pandey, S.; Calvey, G.; Katz, A.M.; Malla, T.N.; Koua, F.H.M.; Martin-Garcia, J.M.; Poudyal, I.; Yang, J.-H.; Vakili, M.; Yefanov, O.; Zielinski, K.A.; Bajt, S.; Awel, S.; Doerner, K.; Frank, M.; Gelisio, L.; Jernigan, R.; Kirkwood, H.; Kloos, M.; Koliyadu, J.; Mariani, V.; Miller, M.D.; Mills, G.; Nelson, G.; Olmos Jr., J.L.; Sadri, A.; Sato, T.; Tolstikova, A.; Xu, W.; Ourmazd, A.; Spence, J.H.C.; Schwander, P.; Barty, A.; Chapman, H.N.; Fromme, P.; Mancuso, A.P.; Phillips Jr, G.N.; Bean, R.; Pollack, L.; Schmidt, M.

doi:10.1107/S2052252521008125

Figure 1
The structures of BlaC and the ligands investigated here. (a) Structure of BlaC in the orthorhombic crystal form. The four subunits of BlaC are shown in red (A), green (B), blue (C) and yellow (D). The red dotted box shows the position of the active site. A phosphate (P_i) is present in all active sites. The catalytically active Ser70 is marked in subunits B and D. (b) The chemical structure of ceftriaxone (CEF). The leaving group (dioxotriazine; the double tilde shows the cleaved bond) and the thiazole ring are marked. (c) The chemical structure of sulbactam (SUB). (d) The covalently bound trans-EN. Ser70 of BlaC opens the β-lactam ring of SUB. The structure rearranges to a trans-enamine. This inactivates BlaC.

IUCrJ

Volume 8| Part 6| November 2021| Pages 878-895

ISSN: 2052-2525

https://doi.org/10.1107/S2052252521008125

BIOLOGY | MEDICINE

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