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We have elucidated the crystal structure of PgQC at 1.95\u00a0\u00c5 resolution in unbound and in inhibitor-complexed forms. The structural characterization of PgQC confirmed that PgQC displays a mammalian fold rather than a bacterial fold. Our biochemical characterization indicates that PgQC uses a mammalian-like catalytic mechanism enabled by the residues Asp<jats:sup>149<\/jats:sup>, Glu<jats:sup>182<\/jats:sup>, Asp<jats:sup>183<\/jats:sup>, Asp<jats:sup>218<\/jats:sup>, Asp<jats:sup>267<\/jats:sup> and His<jats:sup>299<\/jats:sup>. In addition, we could observe that a non-conserved Trp<jats:sup>193<\/jats:sup> may drive differences in the binding affinity of ligands which might be useful for drug development. With a screening of a small molecule library, we have identified a benzimidazole derivative rendering PgQC inhibition in the low micromolar range that might be amenable for further medicinal chemistry development.<\/jats:p>","DOI":"10.1515\/hsz-2020-0298","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T22:53:08Z","timestamp":1617835988000},"page":"759-768","source":"Crossref","is-referenced-by-count":2,"title":["Structural and kinetic characterization of <i>Porphyromonas gingivalis<\/i> glutaminyl cyclase"],"prefix":"10.1515","volume":"402","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-0643","authenticated-orcid":false,"given":"Sebastiaan","family":"Lamers","sequence":"first","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoli","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yili","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Health and Environmental Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Advanced Research Institute, Chinese Academy of Sciences , Shanghai 201204 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxwell","family":"Lukman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-9615","authenticated-orcid":false,"given":"David","family":"Ruiz-Carrillo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences , School of Science, Xi\u2019an Jiaotong-Liverpool University , Suzhou , Jiangsu 215123 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"2023040406521603237_j_hsz-2020-0298_ref_001_w2aab3b7c13b1b6b1ab2b2b1Aa","doi-asserted-by":"crossref","unstructured":"Abraham, G.N., and Podell, D.N. 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