{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:34:30Z","timestamp":1789716870460,"version":"4.0.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2006,7,15]],"date-time":"2006-07-15T00:00:00Z","timestamp":1152921600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2006,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Legionella pneumophila<\/jats:italic>is a gram-negative facultative intracellular human pathogen that can cause fatal Legionnaires' disease. Polypeptide deformylase (PDF) is a novel broad-spectrum antibacterial target, and reports of inhibitors of PDF with potent activities against<jats:italic>L. pneumophila<\/jats:italic>have been published previously. Here, we report the identification of not one but three putative<jats:italic>pdf<\/jats:italic>genes,<jats:italic>pdfA<\/jats:italic>,<jats:italic>pdfB<\/jats:italic>, and<jats:italic>pdfC<\/jats:italic>, in the complete genome sequences of three strains of<jats:italic>L. pneumophila<\/jats:italic>. Phylogenetic analysis showed that<jats:italic>L. pneumophila<\/jats:italic>PdfA is most closely related to the commonly known \u03b3-proteobacterial PDFs encoded by the gene<jats:italic>def.<\/jats:italic>PdfB and PdfC are more divergent and do not cluster with any specific bacterial or eukaryotic PDF. All three putative<jats:italic>pdf<\/jats:italic>genes from<jats:italic>L. pneumophila<\/jats:italic>strain Philadelphia 1 have been cloned, and their encoded products have been overexpressed in<jats:italic>Escherichia coli<\/jats:italic>and purified. Enzymatic characterization shows that the purified PDFs with Ni<jats:sup>2+<\/jats:sup>substituted are catalytically active and able to remove the N-formyl group from several synthetic polypeptides, although they appear to have different substrate specificities. Surprisingly, while PdfA and PdfB with Zn<jats:sup>2+<\/jats:sup>substituted are much less active than the Ni<jats:sup>2+<\/jats:sup>forms of each enzyme, PdfC with Zn<jats:sup>2+<\/jats:sup>substituted was as active as the Ni<jats:sup>2+<\/jats:sup>form for the fMA substrate and exhibited substrate specificity different from that of Ni<jats:sup>2+<\/jats:sup>PdfC. Furthermore, the catalytic activities of these enzymes are potently inhibited by a known small-molecule PDF inhibitor, BB-3497, which also inhibits the extracellular growth of<jats:italic>L. pneumophila<\/jats:italic>. These results indicate that even though<jats:italic>L. pneumophila<\/jats:italic>has three PDFs, they can be effectively inhibited by PDF inhibitors which can, therefore, have potent anti-<jats:italic>L. pneumophila<\/jats:italic>activity.<\/jats:p>","DOI":"10.1128\/jb.00866-05","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T23:17:58Z","timestamp":1151709478000},"page":"5249-5257","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Phylogenomic and Biochemical Characterization of Three<i>Legionella pneumophila<\/i>Polypeptide Deformylases"],"prefix":"10.1128","volume":"188","author":[{"given":"Jianzhong","family":"Huang","sequence":"first","affiliation":[{"name":"Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn S.","family":"Van Aller","sequence":"additional","affiliation":[{"name":"Enzymology and Mechanistic Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy N.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Gene Expression and Protein Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Kerrigan","sequence":"additional","affiliation":[{"name":"Gene Expression and Protein Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Schyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Gene Expression and Protein Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Trulli","sequence":"additional","affiliation":[{"name":"Gene Expression and Protein Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Lai","sequence":"additional","affiliation":[{"name":"Enzymology and Mechanistic Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Holmes","sequence":"additional","affiliation":[{"name":"Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Aubart","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Bioinformatics, GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, Pennsylvania 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zalacain","sequence":"additional","affiliation":[{"name":"Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_2_3_2","first-page":"809","volume":"5","year":"2004","unstructured":"Boularot, A., C. Giglione, I. Artaud, and T. Meinnel. 2004. Structure-activity relationship analysis and therapeutic potential of peptide deformylase inhibitors. Curr. Opin. Investig. Drugs 5 : 809-822.","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF02605418","volume":"1","year":"1978","unstructured":"Brenner, D. J., A. Steigerwalt, J. E. Weaver, J. E. McDade, J. C. Feeley, and M. Mandel. 1978. 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