{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:56:55Z","timestamp":1790251015679,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T00:00:00Z","timestamp":1555632000000},"content-version":"vor","delay-in-days":383,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases, NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Health and Human Services"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN-148463"],"award-info":[{"award-number":["FRN-148463"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Research Chair in Antibiotic Biochemistry"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Chemical Biology"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.chembiol.2018.01.009","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T18:21:43Z","timestamp":1517509303000},"page":"403-412.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":70,"title":["Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action"],"prefix":"10.1016","volume":"25","author":[{"given":"Kalinka","family":"Koteva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne K.","family":"Kelso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Surette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley L.","family":"Zubyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Ejim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Stogios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Savchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard D.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.chembiol.2018.01.009_bib1","doi-asserted-by":"crossref","first-page":"e0162578","DOI":"10.1371\/journal.pone.0162578","article-title":"Mechanism of rifampicin inactivation in Nocardia farcinica","volume":"11","author":"Abdelwahab","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.chembiol.2018.01.009_bib2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib3","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1128\/AAC.41.1.218","article-title":"Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic","volume":"41","author":"Andersen","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.chembiol.2018.01.009_bib4","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.tube.2010.02.001","article-title":"Rifamycins\u2014obstacles and opportunities","volume":"90","author":"Aristoff","year":"2010","journal-title":"Tuberculosis"},{"key":"10.1016\/j.chembiol.2018.01.009_bib5","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1073\/pnas.0711939105","article-title":"Rifamycin antibiotic resistance by ADP-ribosylation: structure and diversity of Arr","volume":"105","author":"Baysarowich","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2018.01.009_bib6","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1021\/bi8023509","article-title":"Crystal structure of Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin biosynthetic pathway","volume":"48","author":"Beam","year":"2009","journal-title":"Biochemistry"},{"key":"10.1016\/j.chembiol.2018.01.009_bib7","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s10096-007-0378-1","article-title":"Rifampin as adjuvant treatment of Gram-positive bacterial infections: a systematic review of comparative clinical trials","volume":"26","author":"Bliziotis","year":"2007","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"10.1016\/j.chembiol.2018.01.009_bib8","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature17042","article-title":"Antibacterial drug discovery in the resistance era","volume":"529","author":"Brown","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.chembiol.2018.01.009_bib9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1107\/S0907444910051218","article-title":"Improvement of molecular-replacement models with Sculptor","volume":"67","author":"Bunkoczi","year":"2011","journal-title":"Acta Crystallogr. Section D Biol. Crystallogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib10","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0092-8674(01)00286-0","article-title":"Structural mechanism for rifampicin inhibition of bacterial RNA polymerase","volume":"104","author":"Campbell","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.chembiol.2018.01.009_bib11","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.1021\/ja00854a048","article-title":"Determination of the solution conformation of rifamycin S and derivatives by nuclear magnetic resonance","volume":"97","author":"Casey","year":"1975","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.chembiol.2018.01.009_bib12","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.chembiol.2016.11.011","article-title":"A common platform for antibiotic dereplication and adjuvant discovery","volume":"24","author":"Cox","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib13","doi-asserted-by":"crossref","first-page":"15601","DOI":"10.3390\/ijms131215601","article-title":"Form follows function: structural and catalytic variation in the class a flavoprotein monooxygenases","volume":"13","author":"Crozier-Reabe","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.chembiol.2018.01.009_bib14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1574-6968.1987.tb02320.x","article-title":"Rifampicin inactivation by Rhodococcus and Mycobacterium species","volume":"44","author":"Dabbs","year":"1987","journal-title":"FEMS Microbiol. Lett."},{"issue":"Suppl 1","key":"10.1016\/j.chembiol.2018.01.009_bib15","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1086\/518155","article-title":"Therapy for and prevention of traveler's diarrhea","volume":"45","author":"DuPont","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.chembiol.2018.01.009_bib16","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. Section D Biol. Crystallogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib17","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1016\/S0021-9258(17)33523-8","article-title":"Flavin-oxygen derivatives involved in hydroxylation by p-hydroxybenzoate hydroxylase","volume":"251","author":"Entsch","year":"1976","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.chembiol.2018.01.009_bib18","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.chembiol.2015.05.017","article-title":"The tetracycline destructases: a novel family of tetracycline-inactivating enzymes","volume":"22","author":"Forsberg","year":"2015","journal-title":"Chem. Biol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib19","series-title":"Analytical Profiles of Drug Substances","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0099-5428(08)60328-7","article-title":"Rifampicin","author":"Gallo","year":"1976"},{"key":"10.1016\/j.chembiol.2018.01.009_bib20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ja.2009.116","article-title":"Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance","volume":"63","author":"Hoshino","year":"2010","journal-title":"J.\u00a0Antibiot."},{"key":"10.1016\/j.chembiol.2018.01.009_bib21","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jmb.2007.06.087","article-title":"Crystal structures of two aromatic hydroxylases involved in the early tailoring steps of angucycline biosynthesis","volume":"372","author":"Koskiniemi","year":"2007","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib22","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1107\/S0907444904026460","article-title":"Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions","volume":"60","author":"Krissinel","year":"2004","journal-title":"Acta Crystallogr. Section D Biol. Crystallogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib23","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of macromolecular assemblies from crystalline state","volume":"372","author":"Krissinel","year":"2007","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib24","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein\u00a0interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.chembiol.2018.01.009_bib25","doi-asserted-by":"crossref","first-page":"21553","DOI":"10.1074\/jbc.M116.745315","article-title":"The structure of the antibiotic deactivating, N-hydroxylating rifampicin monooxygenase","volume":"291","author":"Liu","year":"2016","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.chembiol.2018.01.009_bib26","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000220462","article-title":"Rifampicin: a new orally active rifamycin","volume":"11","author":"Maggi","year":"1966","journal-title":"Chemotherapy"},{"key":"10.1016\/j.chembiol.2018.01.009_bib27","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1107\/S0907444906019949","article-title":"HKL-3000: the integration of data reduction and structure solution\u2014from diffraction images to an initial model in minutes","volume":"62","author":"Minor","year":"2006","journal-title":"Acta Crystallogr. Section D Biol. Crystallogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib28","doi-asserted-by":"crossref","first-page":"11829","DOI":"10.1021\/bi0506066","article-title":"Tigecycline is modified by the flavin-dependent monooxygenase TetX","volume":"44","author":"Moore","year":"2005","journal-title":"Biochemistry"},{"key":"10.1016\/j.chembiol.2018.01.009_bib29","series-title":"The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals","author":"O'Neil","year":"2001"},{"key":"10.1016\/j.chembiol.2018.01.009_bib30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nchembio.2376","article-title":"Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes","volume":"13","author":"Park","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib31","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1073\/pnas.1523614113","article-title":"Structural basis of rifampin inactivation by rifampin phosphotransferase","volume":"113","author":"Qi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2018.01.009_bib32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1054\/tuld.1998.0002","article-title":"Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update","volume":"79","author":"Ramaswamy","year":"1998","journal-title":"Tubercle Lung Dis."},{"key":"10.1016\/j.chembiol.2018.01.009_bib33","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1021\/ja00534a007","article-title":"Oxygen-18 isotope effect in carbon-13 nuclear magnetic resonance spectroscopy. 2. The effect of structure","volume":"102","author":"Risley","year":"1980","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.chembiol.2018.01.009_bib34","doi-asserted-by":"crossref","first-page":"15311","DOI":"10.1073\/pnas.0707190104","article-title":"Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC","volume":"104","author":"Ryan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2018.01.009_bib35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0022-2860(00)00871-1","article-title":"NMR studies of some rifamycins","volume":"563","author":"Santos","year":"2001","journal-title":"J.\u00a0Mol. Struct."},{"key":"10.1016\/j.chembiol.2018.01.009_bib36","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.chembiol.2018.01.009_bib37","doi-asserted-by":"crossref","first-page":"5061","DOI":"10.1128\/AAC.01166-12","article-title":"Characterization of a rifampin-inactivating glycosyltransferase from a screen of environmental actinomycetes","volume":"56","author":"Spanogiannopoulos","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.chembiol.2018.01.009_bib38","doi-asserted-by":"crossref","first-page":"7102","DOI":"10.1073\/pnas.1402358111","article-title":"A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria","volume":"111","author":"Spanogiannopoulos","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2018.01.009_bib39","doi-asserted-by":"crossref","first-page":"11343","DOI":"10.1038\/ncomms11343","article-title":"Rifampin phosphotransferase is an unusual antibiotic resistance kinase","volume":"7","author":"Stogios","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.chembiol.2018.01.009_bib40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.pep.2005.01.016","article-title":"Protein production by auto-induction in high density shaking cultures","volume":"41","author":"Studier","year":"2005","journal-title":"Protein Expr. Purif."},{"key":"10.1016\/j.chembiol.2018.01.009_bib41","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jbiotec.2006.03.044","article-title":"Flavoprotein monooxygenases, a diverse class of oxidative biocatalysts","volume":"124","author":"van Berkel","year":"2006","journal-title":"J.\u00a0Biotechnol."},{"key":"10.1016\/j.chembiol.2018.01.009_bib42","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1039\/c39800000183","article-title":"Biosynthesis of averufin by Aspergillus parasiticus; detection of 18O-label by 13C-N.M.R. isotope shifts","author":"Vederas","year":"1980","journal-title":"J.\u00a0Chem. Soc. Chem. Commun."},{"key":"10.1016\/j.chembiol.2018.01.009_bib43","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0021-9673(01)93925-1","article-title":"Liquid chromatographic-mass spectrometric studies on rifamycin antibiotics","volume":"474","author":"Vekey","year":"1989","journal-title":"J.\u00a0Chromatogr."},{"key":"10.1016\/j.chembiol.2018.01.009_bib44","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.febslet.2011.03.012","article-title":"Structural basis for a new tetracycline resistance mechanism relying on the TetX monooxygenase","volume":"585","author":"Volkers","year":"2011","journal-title":"FEBS Lett."},{"key":"10.1016\/j.chembiol.2018.01.009_bib45","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.addr.2005.04.002","article-title":"Bacterial resistance to antibiotics: enzymatic degradation and modification","volume":"57","author":"Wright","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.chembiol.2018.01.009_bib46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrmicro1614","article-title":"The antibiotic resistome: the nexus of chemical and genetic diversity","volume":"5","author":"Wright","year":"2007","journal-title":"Nat. Rev. Microbiol."}],"container-title":["Cell Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S245194561830031X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S245194561830031X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T19:34:48Z","timestamp":1660419288000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S245194561830031X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["S245194561830031X"],"URL":"https:\/\/doi.org\/10.1016\/j.chembiol.2018.01.009","relation":{},"ISSN":["2451-9456"],"issn-type":[{"value":"2451-9456","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action","name":"articletitle","label":"Article Title"},{"value":"Cell Chemical Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chembiol.2018.01.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}