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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:p>\n                    During microbial infection, mammalian hosts reduce the availability of free metals such as zinc in a process known as nutritional immunity. Pathogens counteract nutritional immunity by expressing gene products that enhance growth in metal-limited conditions. One of the most transcriptionally induced genes in zinc-limited\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Neisseria<\/jats:italic>\n                      gonorrhoeae\n                    <\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ngo1049,<\/jats:italic>\n                    encodes a DUF4198 family protein we have named Zcp. This family of proteins is widely distributed in Gram-negative bacteria. Here, we provide the first structural, biochemical, and functional characterization of a DUF4198 protein. Zcp is a periplasmic, homodimeric substrate-binding protein (SBP), which binds one zinc ion per subunit with submicromolar affinity. We identified a zinc binding pocket in each subunit, composed of three histidine residues. Zcp enables maximal growth of\n                    <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                    in zinc-limited conditions but is dispensable for zinc uptake, in contrast to the cluster A-I SBP ZnuA, which is required for zinc import. The growth defect of\n                    <jats:italic toggle=\"yes\">zcp<\/jats:italic>\n                    mutant\n                    <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                    is rescued by zinc supplementation. Zcp associates with proteins with roles in maintaining cell envelope integrity, and\n                    <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                    lacking\n                    <jats:italic toggle=\"yes\">zcp<\/jats:italic>\n                    is more sensitive to envelope-targeting antimicrobials. Zcp enables infectivity of human epithelial cells and neutrophils by zinc-limited\n                    <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                    . We conclude that\n                    <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                    produces Zcp to buffer periplasmic zinc, which enables ZnuA to balance import of different metals and ensures the bioavailability of zinc for extracytoplasmic zinc-requiring proteins, as part of the coordinated response to host-imposed nutritional immunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426176122","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T17:23:32Z","timestamp":1763573012000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["A periplasmic zinc capture protein enhances the resistance of\n                    <i>Neisseria gonorrhoeae<\/i>\n                    to nutritional immunity"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-123X","authenticated-orcid":false,"given":"Ian K.","family":"Liyayi","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloke Kumar","family":"Bera","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University","place":["West Lafayette"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasiru R.","family":"Perera","sequence":"additional","affiliation":[{"name":"Center for Structural Biology, Vanderbilt University","place":["Nashville"]},{"name":"Department of Biochemistry, Vanderbilt University School of Medicine","place":["Nashville"]},{"name":"Department of Chemistry, Vanderbilt 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