{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:49:30Z","timestamp":1791964170878,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000997","name":"Arnold and Mabel Beckman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:p>Protein quality control in bacteria relies on dynamic chaperone networks that rapidly respond to environmental stresses. In mycobacteria, a central Hsp70 chaperone, DnaK, and its co\u2010chaperones, J\u2010domain proteins (JDPs), play essential roles in the cellular response to stress and antibiotics. Conserved \u201cJ\u2010domain\u201d sequences of JDPs are known to mediate transient interactions with Hsp70s and other protein partners. We have previously shown that a rationally designed proteomimetic of a J\u2010domain is toxic to stressed mycobacterial cells. Here, we aimed to trap J\u2010domain mimetic interaction partners to potentially reveal vulnerabilities in cellular stress\u2010response pathways. To do so, we modified a J\u2010domain proteomimetic of the mycobacterial JDP DnaJ1 (J1C) with a photoaffinity label moiety, resulting in J1C\u2013PAL. In heat\u2010shocked mycobacteria, J1C\u2013PAL crosslinked to DnaK in cells, confirming retention of canonical Hsp70\u2010binding activity under proteotoxic stress. Chemoproteomic profiling revealed additional cellular targets, namely a conditionally essential mycobacterial protein, glutamine synthetase (GS). Biochemical assays demonstrated that J1C\u2013PAL bound GS and inhibited its enzymatic activity. Cellular studies validated that J1C perturbed nitrogen metabolism mediated by GS in mycobacteria. Together, these findings establish J1C\u2013PAL as a cell\u2010permeable chemoproteomic tool for mapping protein targets and uncover a surprising link between a co\u2010chaperone mimetic and bacterial metabolism.<\/jats:p>","DOI":"10.1002\/cbic.70504","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:35:44Z","timestamp":1788201344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Co\u2010Chaperone Mimetic Perturbs Cellular Nitrogen Metabolism in Mycobacteria"],"prefix":"10.1002","volume":"27","author":[{"given":"Brock","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Chemistry New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0989-2565","authenticated-orcid":false,"given":"Tania J.","family":"Lupoli","sequence":"additional","affiliation":[{"name":"Department of Chemistry New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.05.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-025-00890-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cstres.2023.12.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00123-21"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.11.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16932-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2023.102373"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00231"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2134250100"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002251"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02133-16"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00070-19"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.033"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004516"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617644113"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC04284A"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10317"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13844"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.03.006"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14884"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00651"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202300261"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2422640122"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.694012"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/162.3.1045"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.12.003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01019-1"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.69.6.3231-3237.2003"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28034"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-102"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06561.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6348-6363.2001"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02143"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3927-3936.2003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00531-06"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.4c00763"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.5.1042"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2003.10.012"},{"issue":"41","key":"e_1_2_9_41_1","first-page":"E9560","article-title":"ATP Hydrolysis\u2010Coupled Peptide Translocation Mechanism of Mycobacterium Tuberculosis ClpB","volume":"115","author":"Yu H.","year":"2018","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00834a066"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002438h"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2007.08.006"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.21.6573-6584.1999"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/mr.59.4.604-622.1995"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2025.2459336"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3238"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3349"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1149041"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.043828-0"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.10.006"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14682"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00131a010"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819468116"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-6-482"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10341"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2982"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00278"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.1.456-464.2003"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(66)90026-9"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_89"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1011"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200800604"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14615"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.2144\/000113418"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b05525"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b10082"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14070817"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70504","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70504","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:37:18Z","timestamp":1791963438000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":68,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9,14]]}},"alternative-id":["10.1002\/cbic.70504"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70504","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70504"}}