{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:32:05Z","timestamp":1790505125298,"version":"4.1.0"},"reference-count":34,"publisher":"International Union of Crystallography (IUCr)","issue":"2","license":[{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["5T32-DE018381"],"award-info":[{"award-number":["5T32-DE018381"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004948","name":"Michigan Economic Development Corporation","doi-asserted-by":"publisher","award":["085P1000817"],"award-info":[{"award-number":["085P1000817"]}],"id":[{"id":"10.13039\/100004948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006132","name":"US Department of Energy, Office of Science","doi-asserted-by":"publisher","award":["DE-AC02-11357"],"award-info":[{"award-number":["DE-AC02-11357"]}],"id":[{"id":"10.13039\/100006132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr F Struct Biol Commun","Acta Crystallogr F","Acta Crystallogr F Struct Biol Cryst Commun","Acta Cryst F","Acta Cryst F Struct Biol Commun","Acta Cryst Sect F","Acta Cryst Sect F Struct Biol Commun","Acta Crystallogr Sect F","Acta Crystallogr Sect F Struct Biol Commun","Acta Crystallogr Sect F Struct Biol Cryst Commun"],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:p>Enoyl-acyl carrier protein (ACP) reductase II (FabK) is a critical rate-limiting enzyme in the bacterial type II fatty-acid synthesis (FAS II) pathway. FAS II pathway enzymes are markedly disparate from their mammalian analogs in the FAS I pathway in both structure and mechanism. Enzymes involved in bacterial fatty-acid synthesis represent viable drug targets for Gram-negative pathogens, and historical precedent exists for targeting them in the treatment of diseases of the oral cavity. The Gram-negative organism<jats:italic>Porphyromonas gingivalis<\/jats:italic>represents a key causative agent of the costly and highly prevalent disease known as chronic periodontitis, and exclusively expresses FabK as its enoyl reductase enzyme in the FAS-II pathway. Together, these characteristics distinguish<jats:italic>P. gingivalis<\/jats:italic>FabK (<jats:italic>Pg<\/jats:italic>FabK) as an attractive and novel narrow-spectrum antibacterial target candidate.<jats:italic>Pg<\/jats:italic>FabK is a flavoenzyme that is dependent on FMN and NADPH as cofactors for the enzymatic reaction, which reduces the enoyl substrate<jats:italic>via<\/jats:italic>a ping-pong mechanism. Here, the structure of the<jats:italic>Pg<\/jats:italic>FabK enzyme as determined using X-ray crystallography is reported to 1.9\u2005\u00c5 resolution with endogenous FMN fully resolved and the NADPH cofactor partially resolved.<jats:italic>Pg<\/jats:italic>FabK possesses a TIM-barrel motif, and all flexible loops are visible. The determined structure has allowed insight into the structural basis for the NADPH dependence observed in<jats:italic>Pg<\/jats:italic>FabK and the role of a monovalent cation that has been observed in previous studies to be stringently required for FabK activity. The<jats:italic>Pg<\/jats:italic>FabK structure and the insights gleaned from its analysis will facilitate structure-based drug-discovery efforts towards the prevention and treatment of<jats:italic>P. gingivalis<\/jats:italic>infection.<\/jats:p>","DOI":"10.1107\/s2053230x18000262","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T11:38:43Z","timestamp":1516966723000},"page":"105-112","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":13,"title":["Structural characterization of<i>Porphyromonas gingivalis<\/i>enoyl-ACP reductase II (FabK)"],"prefix":"10.1107","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-3625","authenticated-orcid":true,"given":"Kirk E.","family":"Hevener","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D.","family":"Santarsiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8006-5661","authenticated-orcid":true,"given":"Jesse A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teuta","family":"Boci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahila","family":"Mehboob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"rf5002_bb1","doi-asserted-by":"crossref","unstructured":"Bell, J. 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