{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:23:28Z","timestamp":1793201008286,"version":"4.5.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,1,13]]},"abstract":"<jats:p>\n                    Serum paraoxonases (PONs) are a group of enzymes that play a key role in organophosphate (OP) detoxification and in prevention of atherosclerosis. However, their structure and mechanism of action are poorly understood. PONs seem like jacks-of-all-trades, acting on a very wide range of substrates, most of which are of no physiological relevance. Family shuffling and screening lead to the first PON variants that express in a soluble and active form in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    . We describe variants with kinetic parameters similar to those reported for PONs purified from sera and others that show dramatically increased activities. In particular, we have evolved PON1 variants with OP-hydrolyzing activities 40-fold higher than wild type and a specificity switch of &gt;2,000-fold, producing PONs specialized for OP rather than ester hydrolysis. Analysis of the newly evolved variants provides insights into the evolutionary relationships between different family members.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536901100","type":"journal-article","created":{"date-parts":[[2004,1,13]],"date-time":"2004-01-13T13:28:06Z","timestamp":1074000486000},"page":"482-487","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":264,"title":["Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization"],"prefix":"10.1073","volume":"101","author":[{"given":"Amir","family":"Aharoni","sequence":"first","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Gaidukov","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Yagur","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Toker","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Silman","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan S.","family":"Tawfik","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,12,26]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(99)00049-6"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.3957"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-334"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm990436t"},{"key":"e_1_3_2_5_2","first-page":"107","volume":"19","year":"1991","unstructured":"Smolen, A., Eckerson, H., Gan, K., Hailat, N. & La Du, B. 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