{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:09:52Z","timestamp":1790698192605,"version":"4.1.0"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Talent Team Support Initiative for Scientific Research and Innovation Platforms of the Xinjiang Talent Development Fund","award":["XJRCXYCTD2025-2"],"award-info":[{"award-number":["XJRCXYCTD2025-2"]}]},{"name":"Third batch of the ?Tianchi Talent? Young Doctoral Research Grant, Xinjiang Autonomous Region","award":["2025QNBS001"],"award-info":[{"award-number":["2025QNBS001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) continues to represent a significant global health danger, with the bacillus Mycobacterium tuberculosis (Mtb) identified as its causative agent. An essential metabolic helper, Coenzyme A (CoA) engages in multiple core cellular processes that are pivotal for both Mtb survival and its ability to cause disease. The terminal step of CoA biosynthesis is catalyzed by dephospho-CoA kinase CoaE, which phosphorylates dephospho-CoA to generate the active cofactor. However, the molecular mechanisms regulating Mtb CoaE catalytic activity remain poorly understood. Here, AlphaFold 3 was used to predict CoaE model. The Ramachandran plot and ProSA were used to validate the model. Subsequently, we performed molecular docking, followed by site-directed mutagenesis. We found that the S15A, R145A or N175A mutants showed markedly reduced activity, whereas the K14A mutation completely abolished activity. Additionally, deletion of residues 27\u2013101 (\u039427\u2013101) led to a significant loss of function. Our findings offer new insights into the structure and mechanism of Mtb CoaE, a promising target for designing selective antituberculosis agents.<\/jats:p>","DOI":"10.1021\/acsomega.6c05535","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:03:45Z","timestamp":1789502625000},"page":"57346-57353","source":"Crossref","is-referenced-by-count":0,"title":["The Dephospho-CoA\nKinase of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    : Molecular Mechanism and Function"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4588-2353","authenticated-orcid":true,"given":"Dafeng","family":"Liu","sequence":"first","affiliation":[{"name":"Yili Normal University , , , ,","place":["Yining, Xinjiang, China, 835000"]},{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashui","family":"Deng","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Song","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"issue":"10481","key":"2026092911103324200_cit1a","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/S0140-6736(24)02479-6","article-title":"Tuberculosis","volume":"405","author":"Trajman","year":"2025","journal-title":"Lancet"},{"key":"2026092911103324200_cit1b","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s41579-025-01201-x","article-title":"Mycobacterium tuberculosis biology, pathogenicity and\ninteraction with the host","volume":"23","author":"Warner","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"issue":"9","key":"2026092911103324200_cit2a","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/s41579-025-01159-w","article-title":"Ecology, global\ndiversity and evolutionary mechanisms in the Mycobacterium tuberculosis\ncomplex","volume":"23","author":"Goig","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"issue":"2","key":"2026092911103324200_cit2b","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00364-0","article-title":"A clinical practice\nguideline for tuberculous meningitis","volume":"26","author":"Donovan","year":"2026","journal-title":"Lancet\nInfect. Dis."},{"issue":"8","key":"2026092911103324200_cit2c","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/S2213-2600(24)00083-3","article-title":"Effectiveness of preventive treatment among different\nage groups and Mycobacterium tuberculosis infection status: a systematic\nreview and individual-participant data meta-analysis of contact tracing\nstudies","volume":"12","author":"Martinez","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"2026092911103324200_cit2d","doi-asserted-by":"publisher","first-page":"100319","DOI":"10.1016\/j.onehlt.2021.100319","article-title":"Tuberculosis\npatients at the human-animal interface: Potential zooanthroponotic\nand zoonotic transmission","volume":"13","author":"Moyo","year":"2021","journal-title":"One Health"},{"issue":"1","key":"2026092911103324200_cit7e","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/s12917-019-2185-1","article-title":"Reverse zoonotic\ntuberculosis transmission from an emerging Uganda I strain between\npastoralists and cattle in South-Eastern Nigeria","volume":"15","author":"Adesokan","year":"2019","journal-title":"BMC Vet. 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Rev. Microbiol."},{"issue":"6","key":"2026092911103324200_cit3f","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1038\/s41591-025-03742-3","article-title":"Strategies\nfor shortening tuberculosis therapy","volume":"31","author":"Dartois","year":"2025","journal-title":"Nat. Med."},{"issue":"1","key":"2026092911103324200_cit3g","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41572-024-00504-2","article-title":"Multidrug-resistant tuberculosis","volume":"10","author":"Dheda","year":"2024","journal-title":"Nat. Rev. Disease. Primers"},{"issue":"1","key":"2026092911103324200_cit3h","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00141-20","article-title":"Mechanisms of Drug-Induced Tolerance\nin Mycobacterium tuberculosis","volume":"34","author":"Goossens","year":"2020","journal-title":"Clin. Microbiol.\nRev."},{"issue":"2\u20133","key":"2026092911103324200_cit4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.plipres.2005.04.001","article-title":"Coenzyme A:\nBack in action","volume":"44","author":"Leonardi","year":"2005","journal-title":"Prog. Lipid Res."},{"issue":"6","key":"2026092911103324200_cit5a","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021390","article-title":"Insights into the Regulatory Characteristics\nof the Mycobacterial Dephosphocoenzyme A Kinase: Implications for\nthe Universal CoA Biosynthesis Pathway","volume":"6","author":"Walia","year":"2011","journal-title":"PLoS\nOne"},{"issue":"1","key":"2026092911103324200_cit5b","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015228","article-title":"Identification of Critical\nResidues of the Mycobacterial Dephosphocoenzyme A Kinase by Site-Directed\nMutagenesis","volume":"6","author":"Walia","year":"2011","journal-title":"PLoS One"},{"issue":"1","key":"2026092911103324200_cit6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/1752-0509-2-109","article-title":"targetTB:\nA target identification\npipeline for Mycobacterium tuberculosis through an interactome, reactome\nand genome-scale structural analysis","volume":"2","author":"Raman","year":"2008","journal-title":"BMC Syst.\nBiol."},{"issue":"10","key":"2026092911103324200_cit7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007645","article-title":"The Role of\nUPF0157 in the Folding\nof M. tuberculosis Dephosphocoenzyme A Kinase and the Regulation of\nthe Latter by CTP","volume":"4","author":"Walia","year":"2009","journal-title":"PLoS One"},{"issue":"8016","key":"2026092911103324200_cit8a","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate\nstructure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"issue":"8042","key":"2026092911103324200_cit8b","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08416-7","article-title":"Addendum:\nAccurate structure prediction of biomolecular interactions with AlphaFold\n3","volume":"636","author":"Abramson","year":"2024","journal-title":"Nature"},{"issue":"2","key":"2026092911103324200_cit9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed\nand accuracy of\ndocking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"issue":"5","key":"2026092911103324200_cit10a","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/nprot.2016.051","article-title":"Computational protein\u2013ligand\ndocking and virtual drug screening with the AutoDock suite","volume":"11","author":"Forli","year":"2016","journal-title":"Nat. Protoc."},{"issue":"6","key":"2026092911103324200_cit10b","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/jcc.20634","article-title":"A semiempirical\nfree energy force field with charge-based desolvation","volume":"28","author":"Huey","year":"2007","journal-title":"J. Comput. Chem."},{"issue":"11","key":"2026092911103324200_cit11","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00420-22","article-title":"Dephospho-Coenzyme\nA\nKinase Is an Exploitable Drug Target against Plasmodium falciparum:\nIdentification of Selective Inhibitors by High-Throughput Screening\nof a Large Chemical Compound Library","volume":"66","author":"Nurkanto","year":"2022","journal-title":"Antimicrob.\nAgents Chemother."},{"issue":"4","key":"2026092911103324200_cit12a","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01146-19","article-title":"Identification of Dephospho-Coenzyme A (Dephospho-CoA) Kinase in\nThermococcus kodakarensis and Elucidation of the Entire CoA Biosynthesis\nPathway in Archaea","volume":"10","author":"Shimosaka","year":"2019","journal-title":"mBio"},{"key":"2026092911103324200_cit12b","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fmicb.2018.02902","article-title":"Biochemical, Metabolomic, and Genetic Analyses of Dephospho\nCoenzyme A Kinase Involved in Coenzyme A Biosynthesis in the Human\nEnteric Parasite Entamoeba histolytica","volume":"9","author":"Nurkanto","year":"2018","journal-title":"Front.\nMicrobiol."},{"issue":"3","key":"2026092911103324200_cit13","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jsb.2014.10.008","article-title":"Crystal structure of Legionella pneumophila\ndephospho-CoA kinase reveals a non-canonical conformation of P-loop","volume":"188","author":"Gong","year":"2014","journal-title":"J. Struct. Biol."},{"issue":"9","key":"2026092911103324200_cit14","doi-asserted-by":"publisher","first-page":"2774","DOI":"10.1128\/JB.183.9.2774-2778.2001","article-title":"Identification\nof yacE (coaE) as\nthe structural gene for dephosphocoenzyme A kinase in Escherichia\ncoli K-12","volume":"183","author":"Mishra","year":"2001","journal-title":"J. Bacteriol."},{"issue":"13","key":"2026092911103324200_cit15a","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1093\/nar\/gkg556","article-title":"ESPript\/ENDscript: extracting and\nrendering sequence and 3D information from atomic structures of proteins","volume":"31","author":"Gouet","year":"2003","journal-title":"Nucleic Acids Res."},{"issue":"21","key":"2026092911103324200_cit15b","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal\nX version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"issue":"W1","key":"2026092911103324200_cit15c","doi-asserted-by":"publisher","first-page":"W521","DOI":"10.1093\/nar\/gkae241","article-title":"The EMBL-EBI Job Dispatcher sequence analysis tools\nframework in 2024","volume":"52","author":"Madeira","year":"2024","journal-title":"Nucleic Acids Res."},{"issue":"W1","key":"2026092911103324200_cit16","doi-asserted-by":"publisher","first-page":"W320","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering key features in protein structures with the new ENDscript\nserver","volume":"42","author":"Robert","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"12","key":"2026092911103324200_cit17a","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4473","article-title":"PDBsum1: A standalone\nprogram for\ngenerating PDBsum analyses","volume":"31","author":"Laskowski","year":"2022","journal-title":"Protein Sci."},{"issue":"12","key":"2026092911103324200_cit17b","doi-asserted-by":"publisher","first-page":"D292","DOI":"10.1093\/nar\/gkt940","article-title":"PDBsum additions","volume":"42","author":"de Beer","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2026092911103324200_cit17c","doi-asserted-by":"publisher","first-page":"D266","DOI":"10.1093\/nar\/gki001","article-title":"PDBsum more: new\nsummaries and analyses of the known 3D structures of proteins and\nnucleic acids","volume":"33","author":"Laskowski","year":"2005","journal-title":"Nucleic Acids Res."},{"issue":"Database","key":"2026092911103324200_cit17d","doi-asserted-by":"publisher","first-page":"D355","DOI":"10.1093\/nar\/gkn860","article-title":"PDBsum new things","volume":"37","author":"Laskowski","year":"2009","journal-title":"Nucleic Acids\nRes"},{"issue":"1","key":"2026092911103324200_cit17e","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/pro.3289","article-title":"PDBsum:\nStructural summaries of PDB entries","volume":"27","author":"Laskowski","year":"2018","journal-title":"Protein\nScience"},{"key":"2026092911103324200_cit18","doi-asserted-by":"publisher","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: interactive web service for the recognition\nof errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"issue":"35","key":"2026092911103324200_cit19a","doi-asserted-by":"publisher","first-page":"39763","DOI":"10.1021\/acsomega.5c03423","article-title":"Study on the Functional Characterization\nof 9-epi-Caryophyllene Synthase from Lavandula x intermedia (Lavandin)","volume":"10","author":"Liu","year":"2025","journal-title":"ACS Omega"},{"key":"2026092911103324200_cit19b","doi-asserted-by":"publisher","first-page":"106838","DOI":"10.1016\/j.pep.2025.106838","article-title":"The long chain fatty acid-CoA ligase\nVraA plays a regulatory role in vancomycin resistance in Staphylococcus\naureus","volume":"238","author":"Liu","year":"2026","journal-title":"Protein Expression Purif."},{"key":"2026092911103324200_cit19c","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fpls.2024.1497345","article-title":"Insights into the functional mechanisms of three terpene synthases\nfrom Lavandula angustifolia (Lavender)","volume":"15","author":"Liu","year":"2024","journal-title":"Front.\nPlant Sci."},{"key":"2026092911103324200_cit19d","doi-asserted-by":"publisher","first-page":"140195","DOI":"10.1016\/j.ijbiomac.2025.140195","article-title":"Insights into the functional\nmechanisms of the sesquiterpene synthase GEAS and GERDS in lavender","volume":"299","author":"Liu","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"2026092911103324200_cit19e","doi-asserted-by":"publisher","first-page":"106520","DOI":"10.1016\/j.pep.2024.106520","article-title":"Expression,\npurification and characterization of CTP synthase PyrG in Staphylococcus\naureus","volume":"221","author":"Liu","year":"2024","journal-title":"Protein Expression Purif."},{"issue":"16","key":"2026092911103324200_cit20a","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4\nand AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"2026092911103324200_cit20b","doi-asserted-by":"publisher","first-page":"1863671","DOI":"10.3389\/fmicb.2026.1863671","article-title":"Molecular insights into the functional mechanism of phosphoserine\nphosphatase SerB2 in Mycobacterium tuberculosis","volume":"17","author":"Liu","year":"2026","journal-title":"Front. Microbiol."},{"issue":"18","key":"2026092911103324200_cit21a","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.2174\/1568026617666170130110827","article-title":"A Practical Guide to Molecular Docking and Homology\nModelling for Medicinal Chemists","volume":"17","author":"Lohning","year":"2017","journal-title":"Curr. Top.\nMed. Chem."},{"issue":"2","key":"2026092911103324200_cit21b","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1021\/acs.jcim.8b00545","article-title":"Comparative Assessment of Scoring\nFunctions: The CASF-2016 Update","volume":"59","author":"Su","year":"2019","journal-title":"J. Chem. Inf.\nModel."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c05535","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/38\/57346\/68521997\/acsomega.6c05535.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/38\/57346\/68521997\/acsomega.6c05535.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:44:54Z","timestamp":1790696694000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/38\/57346\/5430646\/The-Dephospho-CoA-Kinase-of-Mycobacterium"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":49,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,15]]},"published-print":{"date-parts":[[2026,9,29]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c05535","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}