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The superbug status of\n                    <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n                    necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of\n                    <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n                    anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-\u00c5 and 2.35-\u00c5 resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC\n                    <jats:sub>50<\/jats:sub>\n                    value of C7-3 and C7-3m2 against anaerobically grown\n                    <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n                    was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development.\n                  <\/jats:p>","DOI":"10.1128\/aac.00186-17","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T20:30:26Z","timestamp":1496694626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Peptide Inhibitors Targeting the Neisseria gonorrhoeae Pivotal Anaerobic Respiration Factor AniA"],"prefix":"10.1128","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-2596","authenticated-orcid":false,"given":"Aleksandra E.","family":"Sikora","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob V.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan W.","family":"Passow","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Romaine","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard A.","family":"Zielke","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin V.","family":"Korotkov","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143304"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/sti.75.1.3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.965-981.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.spid.2005.06.006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-192807000-00012"},{"key":"e_1_3_3_7_2","first-page":"S32","article-title":"Sexually transmitted diseases and infertility","volume":"21","author":"Westrom LV","year":"1994","unstructured":"Westrom LV . 1994. 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