{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:59:24Z","timestamp":1790881164011,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Nicotinamidases (PncA) catalyze the hydrolysis of nicotinamide to nicotinic acid, a key step in NAD\n                    <jats:sup>+<\/jats:sup>\n                    salvage pathways. In the Lyme disease spirochete\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , the plasmid\u2010encoded gene\n                    <jats:italic>bbe22<\/jats:italic>\n                    encodes a PncA enzyme that is essential for survival in both mammalian and tick hosts. Previous genetic and biochemical studies demonstrated that translation of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    PncA initiates from a rare non\u2010canonical AUU start codon, resulting in a protein that is 24 residues longer than the sequence currently annotated in major databases. Despite these findings, public resources such as UniProt and KEGG still list a truncated protein beginning at residue 36, which lacks part of the N\u2010terminal region required for enzymatic activity. Here we report the crystal structure of full\u2010length\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    PncA determined at 3.2\u2009\u00c5 resolution. The structure reveals the canonical fold of bacterial nicotinamidases and clear electron density for a ligand in the active site consistent with nicotinic acid, the product of the enzymatic reaction. Structural comparison with homologous PncA enzymes demonstrates conservation of the catalytic architecture, including residues involved in substrate binding and catalysis. Importantly, the experimentally determined structure confirms that the longer N\u2010terminal sequence described previously is required for formation of the correct fold and active\u2010site geometry, whereas the truncated annotation is structurally inconsistent with the observed fold and with AlphaFold predictions. Our results provide the first structural characterization of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    PncA and resolve the long\u2010standing annotation discrepancy for\n                    <jats:italic>bbe22<\/jats:italic>\n                    , validating the correct protein sequence and providing the structural basis for nicotinamidase activity in this essential metabolic enzyme.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70268","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T16:41:18Z","timestamp":1778517678000},"page":"1974-1981","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The crystal structure of the\n                    <i>Borrelia burgdorferi<\/i>\n                    nicotinamidase\n                    <scp>BBE22<\/scp>\n                    resolves a long\u2010standing annotation error"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0757-7462","authenticated-orcid":false,"given":"Kalvis","family":"Brangulis","sequence":"first","affiliation":[{"name":"Latvian Biomedical Research and Study Centre  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/37551"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01698.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102958.2003.03452.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.051706\u20100"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0296127"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906022116"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0350503"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102958.2011.07799.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi1012436"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200903407"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4519"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"}],"container-title":["FEBS 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