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To overcome the computational scaling limits that have traditionally hindered NMR crystallography in large systems, we use an accelerated workflow in which machine-learning interatomic potentials enable efficient geometry refinement prior to density functional theory chemical shift calculations. For Toho-1, quantitative analysis of the active-site chemical shifts and chemical shift tensors using this hybrid protocol reveals that the key active-site side chains retain their canonical charge states in the presence of avibactam, with Lys73 and Lys234 protonated and positively charged, and Glu166 deprotonated and poised to function as a general base. Contrary to recent proposals suggesting that avibactam inhibits by suppressing essential proton transfers through p\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>a<\/jats:sub>\n                    perturbations, our data point to a more direct chemical origin arising from the intrinsic resistance of the Ser70-avibactam carbamoyl linkage to hydrolysis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2616547123","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:55:17Z","timestamp":1789494917000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["NMR crystallography reveals active-site protonation states of Toho-1 \u03b2-lactamase in complex with avibactam"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8319-4413","authenticated-orcid":false,"given":"Christopher G.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-7377","authenticated-orcid":false,"given":"Songlin","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Wisconsin-Madison","place":["Madison"]},{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-5958","authenticated-orcid":false,"given":"Patricia S.","family":"Langan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qz5mb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Oak Ridge National Laboratory, Neutron Scattering Science Division","place":["Oak Ridge"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F.","family":"Thome","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1144-0677","authenticated-orcid":false,"given":"Sebastian A.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob B.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rittik K.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6486-8007","authenticated-orcid":false,"given":"Kevin L.","family":"Weiss","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qz5mb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Oak Ridge National Laboratory, Neutron Scattering Science Division","place":["Oak Ridge"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-2580","authenticated-orcid":false,"given":"Gregory J. O.","family":"Beran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2342-049X","authenticated-orcid":false,"given":"Leighton","family":"Coates","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qz5mb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Oak Ridge National Laboratory, Neutron Scattering Science Division","place":["Oak Ridge"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"Rienstra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Wisconsin-Madison","place":["Madison"]},{"id":[{"id":"https:\/\/ror.org\/01y2jtd41","id-type":"ROR","asserted-by":"publisher"}],"name":"National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2607-9875","authenticated-orcid":false,"given":"Leonard J.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Riverside","place":["Riverside"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.2165\/11318430-000000000-00000"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc8892"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-013-0640-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.10.2269"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1123-1129.2006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl483"},{"key":"e_1_3_4_7_2","first-page":"417","article-title":"An update on newer \u03b2-lactamases","volume":"126","author":"Gupta V.","year":"2007","unstructured":"V. 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