{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:44Z","timestamp":1792166324880,"version":"4.4.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,8,6]]},"abstract":"<jats:p>\n                    Plantazolicin (PZN), a polyheterocyclic,\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u03b1<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>,N<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u03b1<\/jats:italic>\n                    <\/jats:sup>\n                    -dimethylarginine\u2013containing antibiotic, harbors remarkably specific bactericidal activity toward strains of\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    , the causative agent of anthrax. Previous studies demonstrated that genetic deletion of the\n                    <jats:italic>S<\/jats:italic>\n                    -adenosyl-\n                    <jats:sc>l<\/jats:sc>\n                    -methionine\u2013dependent methyltransferase from the PZN biosynthetic gene cluster results in the formation of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in vitro reconstitution, mutational analysis, and X-ray crystallographic structure of the PZN methyltransferase. Unlike all other known small molecule methyltransferases, which act upon diverse substrates in vitro, the PZN methyltransferase is uncharacteristically limited in substrate scope and functions only on desmethylPZN and close derivatives. The crystal structures of two related PZN methyltransferases, solved to 1.75 \u00c5 (\n                    <jats:italic>Bacillus amyloliquefaciens<\/jats:italic>\n                    ) and 2.0 \u00c5 (\n                    <jats:italic>Bacillus pumilus<\/jats:italic>\n                    ), reveal a deep, narrow cavity, putatively functioning as the binding site for desmethylPZN. The narrowness of this cavity provides a framework for understanding the molecular basis of the extreme substrate selectivity. Analysis of a panel of point mutations to the methyltransferase from\n                    <jats:italic>B. amyloliquefaciens<\/jats:italic>\n                    allowed the identification of residues of structural and catalytic importance. These findings further our understanding of one set of orthologous enzymes involved in thiazole\/oxazole-modified microcin biosynthesis, a rapidly growing sector of natural products research.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1306101110","type":"journal-article","created":{"date-parts":[[2013,7,22]],"date-time":"2013-07-22T23:53:19Z","timestamp":1374537199000},"page":"12954-12959","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Structural and functional insight into an unexpectedly selective\n                    <i>N<\/i>\n                    -methyltransferase involved in plantazolicin biosynthesis"],"prefix":"10.1073","volume":"110","author":[{"given":"Jaeheon","family":"Lee","sequence":"first","affiliation":[{"name":"Institute for Genomic Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hao","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Departments of bBiochemistry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Blair","sequence":"additional","affiliation":[{"name":"Chemistry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel O.","family":"Melby","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Chemistry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinayak","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Center for Biophysics and Computational Biology, University of Illinois at Urbana\u2013Champaign, Urbana, IL 61801"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon J.","family":"Burkhart","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Chemistry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish K.","family":"Nair","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Departments of bBiochemistry,"},{"name":"Center for Biophysics and Computational Biology, University of Illinois at Urbana\u2013Champaign, Urbana, IL 61801"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Institute for Genomic Biology,"},{"name":"Chemistry, and"},{"name":"Microbiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,7,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1128\/JB.00784-10","article-title":"Plantazolicin, a novel microcin B17\/streptolysin S-like natural product from Bacillus amyloliquefaciens FZB42","volume":"193","author":"Scholz R","year":"2011","unstructured":"R Scholz, et al., Plantazolicin, a novel microcin B17\/streptolysin S-like natural product from Bacillus amyloliquefaciens FZB42. J Bacteriol 193, 215\u2013224 (2011).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1021\/ol200809m","article-title":"Plantazolicin A and B: Structure elucidation of ribosomally synthesized thiazole\/oxazole peptides from Bacillus amyloliquefaciens FZB42","volume":"13","author":"Kalyon B","year":"2011","unstructured":"B Kalyon, et al., Plantazolicin A and B: Structure elucidation of ribosomally synthesized thiazole\/oxazole peptides from Bacillus amyloliquefaciens FZB42. Org Lett 13, 2996\u20132999 (2011).","journal-title":"Org Lett"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1021\/cb200339d","article-title":"Structure determination and interception of biosynthetic intermediates for the plantazolicin class of highly discriminating antibiotics","volume":"6","author":"Molohon KJ","year":"2011","unstructured":"KJ Molohon, et al., Structure determination and interception of biosynthetic intermediates for the plantazolicin class of highly discriminating antibiotics. ACS Chem Biol 6, 1307\u20131313 (2011).","journal-title":"ACS Chem Biol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"5879","DOI":"10.1073\/pnas.0801338105","article-title":"Discovery of a widely distributed toxin biosynthetic gene cluster","volume":"105","author":"Lee SW","year":"2008","unstructured":"SW Lee, et al., Discovery of a widely distributed toxin biosynthetic gene cluster. Proc Natl Acad Sci USA 105, 5879\u20135884 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1039\/C2NP20085F","article-title":"Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature","volume":"30","author":"Arnison PG","year":"2013","unstructured":"PG Arnison, et al., Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature. Nat Prod Rep 30, 108\u2013160 (2013).","journal-title":"Nat Prod Rep"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.cbpa.2011.02.027","article-title":"Thiazole\/oxazole-modified microcins: Complex natural products from ribosomal templates","volume":"15","author":"Melby JO","year":"2011","unstructured":"JO Melby, NJ Nard, DA Mitchell, Thiazole\/oxazole-modified microcins: Complex natural products from ribosomal templates. Curr Opin Chem Biol 15, 369\u2013378 (2011).","journal-title":"Curr Opin Chem Biol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/cbic.201000196","article-title":"Marine molecular machines: Heterocyclization in cyanobactin biosynthesis","volume":"11","author":"McIntosh JA","year":"2010","unstructured":"JA McIntosh, EW Schmidt, Marine molecular machines: Heterocyclization in cyanobactin biosynthesis. ChemBioChem 11, 1413\u20131421 (2010).","journal-title":"ChemBioChem"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"13250","DOI":"10.1021\/bi980996e","article-title":"ATP\/GTP hydrolysis is required for oxazole and thiazole biosynthesis in the peptide antibiotic microcin B17","volume":"37","author":"Milne JC","year":"1998","unstructured":"JC Milne, AC Eliot, NL Kelleher, CT Walsh, ATP\/GTP hydrolysis is required for oxazole and thiazole biosynthesis in the peptide antibiotic microcin B17. Biochemistry 37, 13250\u201313261 (1998).","journal-title":"Biochemistry"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nchembio.944","article-title":"YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations","volume":"8","author":"Dunbar KL","year":"2012","unstructured":"KL Dunbar, JO Melby, DA Mitchell, YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations. Nat Chem Biol 8, 569\u2013575 (2012).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"5309","DOI":"10.1021\/ja211675n","article-title":"Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase","volume":"134","author":"Melby JO","year":"2012","unstructured":"JO Melby, KL Dunbar, NQ Trinh, DA Mitchell, Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase. J Am Chem Soc 134, 5309\u20135316 (2012).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1021\/bi982975q","article-title":"Cofactor requirements and reconstitution of microcin B17 synthetase: A multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17","volume":"38","author":"Milne JC","year":"1999","unstructured":"JC Milne, et al., Cofactor requirements and reconstitution of microcin B17 synthetase: A multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17. Biochemistry 38, 4768\u20134781 (1999).","journal-title":"Biochemistry"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"16297","DOI":"10.1073\/pnas.1008608107","article-title":"Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides","volume":"107","author":"Claesen J","year":"2010","unstructured":"J Claesen, M Bibb, Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc Natl Acad Sci USA 107, 16297\u201316302 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1128\/JB.00171-11","article-title":"Biosynthesis and regulation of grisemycin, a new member of the linaridin family of ribosomally synthesized peptides produced by Streptomyces griseus IFO 13350","volume":"193","author":"Claesen J","year":"2011","unstructured":"J Claesen, MJ Bibb, Biosynthesis and regulation of grisemycin, a new member of the linaridin family of ribosomally synthesized peptides produced by Streptomyces griseus IFO 13350. J Bacteriol 193, 2510\u20132516 (2011).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1016\/j.febslet.2012.07.050","article-title":"Catalytic promiscuity of a bacterial \u03b1-N-methyltransferase","volume":"586","author":"Zhang Q","year":"2012","unstructured":"Q Zhang, WA van der Donk, Catalytic promiscuity of a bacterial \u03b1-N-methyltransferase. FEBS Lett 586, 3391\u20133397 (2012).","journal-title":"FEBS Lett"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ab.2003.11.014","article-title":"An enzyme-coupled colorimetric assay for S-adenosylmethionine-dependent methyltransferases","volume":"326","author":"Hendricks CL","year":"2004","unstructured":"CL Hendricks, JR Ross, E Pichersky, JP Noel, ZS Zhou, An enzyme-coupled colorimetric assay for S-adenosylmethionine-dependent methyltransferases. Anal Biochem 326, 100\u2013105 (2004).","journal-title":"Anal Biochem"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1110\/ps.8.8.1668","article-title":"Escherichia coli maltose-binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused","volume":"8","author":"Kapust RB","year":"1999","unstructured":"RB Kapust, DS Waugh, Escherichia coli maltose-binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused. Protein Sci 8, 1668\u20131674 (1999).","journal-title":"Protein Sci"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"13004","DOI":"10.1074\/jbc.M900802200","article-title":"Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S","volume":"284","author":"Mitchell DA","year":"2009","unstructured":"DA Mitchell, et al., Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S. J Biol Chem 284, 13004\u201313012 (2009).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/cbic.200500504","article-title":"RebG- and RebM-catalyzed indolocarbazole diversification","volume":"7","author":"Zhang C","year":"2006","unstructured":"C Zhang, et al., RebG- and RebM-catalyzed indolocarbazole diversification. ChemBioChem 7, 795\u2013804 (2006).","journal-title":"ChemBioChem"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1021\/ja056231t","article-title":"Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine","volume":"128","author":"Zhang C","year":"2006","unstructured":"C Zhang, RL Weller, JS Thorson, SR Rajski, Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine. J Am Chem Soc 128, 2760\u20132761 (2006).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"17557","DOI":"10.1073\/pnas.1006848107","article-title":"Characterization and structure of DhpI, a phosphonate O-methyltransferase involved in dehydrophos biosynthesis","volume":"107","author":"Lee JH","year":"2010","unstructured":"JH Lee, et al., Characterization and structure of DhpI, a phosphonate O-methyltransferase involved in dehydrophos biosynthesis. Proc Natl Acad Sci USA 107, 17557\u201317562 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.chembiol.2007.07.014","article-title":"Improved mutasynthetic approaches for the production of modified aminocoumarin antibiotics","volume":"14","author":"Anderle C","year":"2007","unstructured":"C Anderle, et al., Improved mutasynthetic approaches for the production of modified aminocoumarin antibiotics. Chem Biol 14, 955\u2013967 (2007).","journal-title":"Chem Biol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0959-440X(02)00391-3","article-title":"SAM (dependent) I AM: The S-adenosylmethionine-dependent methyltransferase fold","volume":"12","author":"Martin JL","year":"2002","unstructured":"JL Martin, FM McMillan, SAM (dependent) I AM: The S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol 12, 783\u2013793 (2002).","journal-title":"Curr Opin Struct Biol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1021\/cb2000567","article-title":"Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling","volume":"6","author":"Islam K","year":"2011","unstructured":"K Islam, W Zheng, H Yu, H Deng, M Luo, Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling. ACS Chem Biol 6, 679\u2013684 (2011).","journal-title":"ACS Chem Biol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1306101110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T05:47:52Z","timestamp":1654580872000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1306101110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,22]]},"references-count":23,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2013,8,6]]}},"alternative-id":["10.1073\/pnas.1306101110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1306101110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,22]]},"assertion":[{"value":"2013-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}