{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:00:41Z","timestamp":1790258441066,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IN209624"],"award-info":[{"award-number":["IN209624"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Activity dysregulation of Abl kinase is the primary cause for chronic myeloid leukemia (CML). Despite extensive characterization, the thermodynamic basis of Abl stability and inhibitor recognition remains incompletely understood. To characterize the cooperative folding organization of Abl and the communication between its structural units, we comprehensively characterized three Abl constructs: the isolated catalytic domain (Abl\n                    <jats:sub>CD<\/jats:sub>\n                    ), the three\u2010domain regulatory construct (Abl\n                    <jats:sub>SH3SH2CD<\/jats:sub>\n                    ), and its phosphorylated form (\n                    <jats:sup>PO4<\/jats:sup>\n                    Abl\n                    <jats:sub>SH3SH2CD<\/jats:sub>\n                    ), using high\u2010resolution calorimetric techniques. DSC revealed that the catalytic domain behaves as a single cooperative unfolding unit, with the SH3\u2013SH2 module in Abl\n                    <jats:sub>SH3SH2CD<\/jats:sub>\n                    exerting a modest stabilizing effect. The catalytic domain decoupled into two transitions in\n                    <jats:sup>PO4<\/jats:sup>\n                    Abl\n                    <jats:sub>SH3SH2CD<\/jats:sub>\n                    , an observation rationalized by the disruption of the interlobe structural bridge formed by the A\u2010loop in the unphosphorylated forms. Imatinib and dasatinib had opposite effects on this decoupling, providing calorimetric evidence for the distinct intradomain reorganizations induced by each inhibitor type. ITC showed that both inhibitors bind with distinct thermodynamic signatures, with a modest effect of the regulatory domains on inhibitor recognition. Imatinib binding involved net proton uptake, consistent with Asp381 protonation required for the DFG\u2010out transition, while dasatinib showed no proton linkage. Phosphorylation\u2010induced reduction in imatinib affinity was driven by a large loss of favorable enthalpy reflecting the energetic cost of displacing the ordered A\u2010loop, while dasatinib affinity remained largely unaffected. These results provide a thermodynamic rationale for the superior potency of dasatinib against activated Abl in CML cells, revealing mechanistic features of kinase regulation not accessible from structural data alone.\n                  <\/jats:p>","DOI":"10.1002\/pro.70791","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:26:14Z","timestamp":1789561574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determinants of Abl kinase stability and drug binding thermodynamics: Role of regulatory domains and phosphorylation"],"prefix":"10.1002","volume":"35","author":[{"given":"Alan","family":"Ju\u00e1rez\u2010Barrag\u00e1n","sequence":"first","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Instituto de Qu\u00edmica Ciudad Universitaria  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8480-0912","authenticated-orcid":false,"given":"J. Alberto","family":"Escobar\u2010C\u00e1zares","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Instituto de Qu\u00edmica Ciudad Universitaria  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2466-5329","authenticated-orcid":false,"given":"Miguel A.","family":"Medina\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Instituto de Qu\u00edmica Ciudad Universitaria  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Tob\u00edas\u2010Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Departamento de Biolog\u00eda Celular y del Desarrollo Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico 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