Heterogeneity in M. tuberculosis β-lactamase inhibition by Sulbactam

Simple item page
dc.citation.articleNumber5507en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber14en_US
dc.contributor.authorMalla, Tek Narsinghen_US
dc.contributor.authorZielinski, Karaen_US
dc.contributor.authorAldama, Luisen_US
dc.contributor.authorBajt, Sasaen_US
dc.contributor.authorFeliz, Denisseen_US
dc.contributor.authorHayes, Brendonen_US
dc.contributor.authorHunter, Marken_US
dc.contributor.authorKupitz, Christopheren_US
dc.contributor.authorLisova, Stellaen_US
dc.contributor.authorKnoska, Jurajen_US
dc.contributor.authorMartin-Garcia, Jose Manuelen_US
dc.contributor.authorMariani, Valerioen_US
dc.contributor.authorPandey, Surajen_US
dc.contributor.authorPoudyal, Ishworen_US
dc.contributor.authorSierra, Raymond G.en_US
dc.contributor.authorTolstikova, Alexandraen_US
dc.contributor.authorYefanov, Oleksandren_US
dc.contributor.authorYoon, Chung Hongen_US
dc.contributor.authorOurmazd, Abbasen_US
dc.contributor.authorFromme, Petraen_US
dc.contributor.authorSchwander, Peteren_US
dc.contributor.authorBarty, Antonen_US
dc.contributor.authorChapman, Henry N.en_US
dc.contributor.authorStojkovic, Emina A.en_US
dc.contributor.authorBatyuk, Alexanderen_US
dc.contributor.authorBoutet, Sébastienen_US
dc.contributor.authorPhillips, George N.en_US
dc.contributor.authorPollack, Loisen_US
dc.contributor.authorSchmidt, Mariusen_US
dc.date.accessioned2024-05-03T15:51:17Zen_US
dc.date.available2024-05-03T15:51:17Zen_US
dc.date.issued2023en_US
dc.description.abstractFor decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals. Here, we report in atomic detail (between 2.2 and 2.7 Å resolution) by room-temperature, time-resolved crystallography with millisecond time-resolution (with timepoints between 3 ms and 700 ms) how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. This was made possible in part by the application of singular value decomposition to the MISC data using a program that remains functional even if unit cell parameters change up to 3 Å during the reaction.en_US
dc.identifier.citationMalla, T. N., Zielinski, K., Aldama, L., Bajt, S., Feliz, D., Hayes, B., Hunter, M., Kupitz, C., Lisova, S., Knoska, J., Martin-Garcia, J. M., Mariani, V., Pandey, S., Poudyal, I., Sierra, R. G., Tolstikova, A., Yefanov, O., Yoon, C. H., Ourmazd, A., … Schmidt, M. (2023). Heterogeneity in M. tuberculosis β-lactamase inhibition by Sulbactam. Nature Communications, 14(1), 5507. https://doi.org/10.1038/s41467-023-41246-1en_US
dc.identifier.digitals41467-023-41246-1en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-023-41246-1en_US
dc.identifier.urihttps://hdl.handle.net/1911/115607en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleHeterogeneity in M. tuberculosis β-lactamase inhibition by Sulbactamen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s41467-023-41246-1.pdf
Size:
2.66 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
BioSciences Publications
Chemistry Publications