{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:23:52Z","timestamp":1789975432105,"version":"4.0.1"},"reference-count":53,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,6,1]]},"abstract":"<jats:p>Neisseria gonorrhoeae is a prolific source of c-type cytochromes. Five of the constitutively expressed cytochromes are predicted, based on in silico analysis of the N. gonorrhoeae genome, to be components of the cytochrome bc1 complex, cytochrome c oxidase cbb3 or periplasmic cytochromes involved in electron transfer reactions typical of a bacterium with a microaerobic physiology. Cytochrome c peroxidase was previously shown to be a lipoprotein expressed only during oxygen-limited growth. The final c-type cytochrome, cytochrome c\u2032, similar to cytochrome c peroxidase, includes a lipobox required for targeting to the outer membrane. Maturation of cytochrome c\u2032 was partially inhibited by globomycin, an antibiotic that specifically inhibits signal peptidase II, resulting in the accumulation of the prolipoprotein in the cytoplasmic membrane. Disruption of the gonococcal cycP gene resulted in an extended lag phase during microaerobic growth in the presence but not in the absence of nitrite, suggesting that cytochrome c\u2032 protects the bacteria from NO generated by nitrite reduction during adaptation to oxygen-limited growth. The cytochrome c\u2032 gene was overexpressed in Escherichia coli and recombinant cytochrome c\u2032 was shown to be targeted to the outer membrane. Spectroscopic evidence is presented showing that gonococcal cytochrome c\u2032 is similar to previously characterized cytochrome c\u2032 proteins and that it binds NO in vitro. The demonstration that two of the seven gonococcal c-type cytochromes fulfil specialized functions and are outer membrane lipoproteins suggests that the localization of these lipoproteins close to the bacterial surface provides effective protection against external assaults from reactive oxygen and reactive nitrogen species.<\/jats:p>","DOI":"10.1042\/bj20041766","type":"journal-article","created":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T09:42:14Z","timestamp":1118137334000},"page":"545-553","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mutational and biochemical analysis of cytochrome <i>c<\/i>\u2032, a nitric oxide-binding lipoprotein important for adaptation of <i>Neisseria gonorrhoeae<\/i> to oxygen-limited growth"],"prefix":"10.1042","volume":"388","author":[{"given":"Susan\u00a0M.","family":"TURNER","sequence":"first","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James\u00a0W.\u00a0B.","family":"MOIR","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, Heslington, York YO10 5YW, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"GRIFFITHS","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy\u00a0W.","family":"OVERTON","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"SMITH","sequence":"additional","affiliation":[{"name":"Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff\u00a0A.","family":"COLE","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,5,24]]},"reference":[{"key":"2021112217433690800_B1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1084\/jem.192.2.227","article-title":"Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro","volume":"192","author":"Vazquez-Torres","year":"2000","journal-title":"J. Exp. Med."},{"key":"2021112217433690800_B2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/0003-9861(92)90433-W","article-title":"Peroxynitrite formation from macrophage-derived nitric oxide","volume":"298","author":"Ischiropoulos","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"2021112217433690800_B3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/0003-9861(92)90434-X","article-title":"Bactericidal activity of peroxynitrite","volume":"298","author":"Zhu","year":"1992","journal-title":"Arch. Biochem. 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Microbiol."},{"key":"2021112217433690800_B7","first-page":"417","article-title":"Identification of heme-containing proteins of Neisseria gonorrhoeae","volume-title":"Pathobiology and Immunobiology of Neisseriaceae, Proceedings of the Eighth Pathogenic Neisseria Conference held at Mexico City","author":"Strange","year":"1994"},{"key":"2021112217433690800_B8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1046\/j.1365-2958.2000.02050.x","article-title":"Identification of transcription activators which regulate gonococcal adaption from aerobic to anaerobic or oxygen-limited growth","volume":"37","author":"Lissenden","year":"2000","journal-title":"Mol. Microbiol."},{"key":"2021112217433690800_B9","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1042\/bj20030088","article-title":"A novel cytochrome c peroxidase from Neisseria gonorrhoeae: a lipoprotein from a Gram-negative bacterium","volume":"373","author":"Turner","year":"2003","journal-title":"Biochem. J."},{"key":"2021112217433690800_B10","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.3181\/00379727-145-38025","article-title":"Factors affecting autolysis of Neisseria gonorrhoeae","volume":"145","author":"Morse","year":"1974","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"2021112217433690800_B11","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1128\/iai.46.1.176-181.1984","article-title":"Anaerobic growth of Neisseria gonorrhoeae coupled to nitrite reduction","volume":"46","author":"Knapp","year":"1984","journal-title":"Infect. Immun."},{"key":"2021112217433690800_B12","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s004380050597","article-title":"The Neisseria gonorrhoeae gene aniA encodes an inducible nitrite reductase","volume":"256","author":"Mellies","year":"1997","journal-title":"Mol. Gen. 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Pathog."},{"key":"2021112217433690800_B15","article-title":"The Pathogenic Anaerobic Bacteria","author":"Smith","year":"1975"},{"key":"2021112217433690800_B16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/clinids\/8.1.86","article-title":"Pelvic inflammatory disease: a review with emphasis on antimicrobial therapy","volume":"8","author":"Burnakis","year":"1986","journal-title":"Rev. Infect. Dis."},{"key":"2021112217433690800_B17","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1172\/JCI115912","article-title":"Regulation of catalase in Neisseria gonorrhoeae","volume":"90","author":"Zheng","year":"1992","journal-title":"J. Clin. Invest."},{"key":"2021112217433690800_B18","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1128\/IAI.68.9.5241-5246.2000","article-title":"Gonococcal nitric oxide reductase is encoded by a single gene, norB, which is required for anaerobic growth and is induced by nitric oxide","volume":"68","author":"Householder","year":"2000","journal-title":"Infect. Immun."},{"key":"2021112217433690800_B19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0014-5793(03)00632-X","article-title":"A Sco homologue plays a role in defence against oxidative stress in pathogenic Neisseria","volume":"546","author":"Seib","year":"2003","journal-title":"FEBS Lett."},{"key":"2021112217433690800_B20","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1128\/JB.184.11.2987-2993.2002","article-title":"Nitric oxide metabolism in Neisseria meningitidis","volume":"184","author":"Anjum","year":"2002","journal-title":"J. Bacteriol."},{"key":"2021112217433690800_B21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/BF00410732","article-title":"Rationalization of properties of nitrate reductases in Rhodopseudomonas capsulata","volume":"137","author":"McEwan","year":"1984","journal-title":"Arch. Microbiol."},{"key":"2021112217433690800_B22","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0003-2697(76)90320-1","article-title":"An efficient and reproducible procedure for the formation of spheroplasts from variously grown Escherichia coli","volume":"74","author":"Witholt","year":"1976","journal-title":"Anal. Biochem."},{"key":"2021112217433690800_B23","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1128\/jb.166.3.1072-1082.1986","article-title":"Identification, immunochemical characterization, and purification of a major lipoprotein antigen associated with the inner (cytoplasmic) membrane of Escherichia coli","volume":"166","author":"Doherty","year":"1986","journal-title":"J. Bacteriol."},{"key":"2021112217433690800_B24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"2021112217433690800_B25","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/0003-2697(76)90067-1","article-title":"An improved staining procedure for the detection of peroxidase activity of cytochrome P-450 on sodium dodecyl sulphate polyacrylamide gels","volume":"75","author":"Thomas","year":"1976","journal-title":"Anal. 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Bacteriol."},{"key":"2021112217433690800_B39","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1073\/pnas.79.7.2255","article-title":"Post-translational modification and processing of Escherichia coli pro-lipoprotein in vitro","volume":"79","author":"Tokunaga","year":"1982","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112217433690800_B40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/mr.57.1.50-108.1993","article-title":"The complete general secretory pathway in Gram-negative bacteria","volume":"57","author":"Pugsley","year":"1993","journal-title":"Microbiol. Rev."},{"key":"2021112217433690800_B41","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1002\/j.1460-2075.1995.tb07342.x","article-title":"A novel periplasmic carrier protein involved in the sorting and transport of Escherichia coli lipoproteins destined for the outer membrane","volume":"14","author":"Matsuyama","year":"1995","journal-title":"EMBO J."},{"key":"2021112217433690800_B42","doi-asserted-by":"crossref","first-page":"6947","DOI":"10.1093\/emboj\/16.23.6947","article-title":"A novel outer membrane lipoprotein, LolB (HemM), involved in the LolA (p20)-dependent localization of lipoproteins to the outer membrane of Escherichia coli","volume":"16","author":"Matsuyama","year":"1997","journal-title":"EMBO J."},{"key":"2021112217433690800_B43","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/35008635","article-title":"A new ABC transporter mediating the detachment of lipid-modified proteins from membranes","volume":"2","author":"Yakushi","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"2021112217433690800_B44","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1128\/JB.184.5.1417-1422.2002","article-title":"Disruption of lolCDE, encoding an ATP-binding cassette transporter, is lethal for Escherichia coli and prevents release of lipoproteins from the inner membrane","volume":"184","author":"Narita","year":"2002","journal-title":"J. Bacteriol."},{"key":"2021112217433690800_B44a","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0092-8674(88)90162-6","article-title":"A single amino acid determinant of the membrane localisation of lipoproteins in E. coli","volume":"53","author":"Yamaguchi","year":"1988","journal-title":"Cell (Cambridge, Mass.)"},{"key":"2021112217433690800_B45","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1046\/j.1365-2958.1999.01647.x","article-title":"Testing the \u2018+2 rule\u2019 for lipoprotein sorting in the Escherichia coli cell envelope with a new genetic selection","volume":"34","author":"Seydel","year":"1999","journal-title":"Mol. Microbiol."},{"key":"2021112217433690800_B46","doi-asserted-by":"crossref","first-page":"47690","DOI":"10.1074\/jbc.M109307200","article-title":"Lipoprotein sorting signals evaluated as the LolA-dependent release of lipoproteins from the cytoplasmic membrane of Escherichia coli","volume":"276","author":"Terada","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021112217433690800_B47","doi-asserted-by":"crossref","first-page":"40408","DOI":"10.1074\/jbc.M307836200","article-title":"Mechanism underlying the inner membrane retention of Escherichia coli lipoproteins caused by Lol avoidance signals","volume":"278","author":"Hara","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021112217433690800_B48","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1128\/JB.184.5.1417-1422.2002","article-title":"Disruption of lolCDE, encoding an ATP-binding cassette transporter, is lethal for Escherichia coli and prevents release of lipoproteins from the inner membrane","volume":"184","author":"Narita","year":"2002","journal-title":"J. Bacteriol."},{"key":"2021112217433690800_B49","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1128\/iai.55.6.1359-1364.1987","article-title":"Induction and repression of outer membrane proteins by anaerobic growth of Neisseria gonorrhoeae","volume":"55","author":"Clark","year":"1987","journal-title":"Infect. 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