{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:55:36Z","timestamp":1791924936721,"version":"4.3.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2004,4,18]],"date-time":"2004-04-18T00:00:00Z","timestamp":1082246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2004,4,18]],"date-time":"2004-04-18T00:00:00Z","timestamp":1082246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2004,5,1]]},"DOI":"10.1038\/nsmb767","type":"journal-article","created":{"date-parts":[[2004,4,21]],"date-time":"2004-04-21T17:45:24Z","timestamp":1082569524000},"page":"412-419","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":556,"title":["Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes"],"prefix":"10.1038","volume":"11","author":[{"given":"Michal","family":"Harel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Aharoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Gaidukov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Brumshtein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Khersonsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Meged","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hay","family":"Dvir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimond B G","family":"Ravelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Toker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Silman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel L","family":"Sussman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan S","family":"Tawfik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2004,4,18]]},"reference":[{"key":"BFnsmb767_CR1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s00210-003-0833-1","volume":"369","author":"DI Draganov","year":"2004","unstructured":"Draganov, D.I. & La Du, B.N. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch. Pharmacol. 369, 78\u2013 88 (2004).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"BFnsmb767_CR2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/35025203","volume":"407","author":"AJ Lusis","year":"2000","unstructured":"Lusis, A.J. Atherosclerosis. Nature 407, 233\u2013 241 (2000).","journal-title":"Nature"},{"key":"BFnsmb767_CR3","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/28406","volume":"394","author":"DM Shih","year":"1998","unstructured":"Shih, D.M. et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284\u2013 287 (1998).","journal-title":"Nature"},{"key":"BFnsmb767_CR4","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/0014-5793(91)80962-3","volume":"286","author":"MI Mackness","year":"1991","unstructured":"Mackness, M.I., Arrol, S. & Durrington, P.N. Paraoxonase prevents accumulation of lipoperoxides in low-density-lipoprotein. FEBS Lett. 286, 152\u2013 154 (1991).","journal-title":"FEBS Lett."},{"key":"BFnsmb767_CR5","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1161\/01.ATV.21.4.542","volume":"21","author":"ST Reddy","year":"2001","unstructured":"Reddy, S.T. et al. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler. Thromb. Vasc. Biol. 21, 542\u2013 547 (2001).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnsmb767_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3540001","volume":"354","author":"L Rodrigo","year":"2001","unstructured":"Rodrigo, L., Mackness, B., Durrington, P.N., Hernandez, A. & Mackness, M.I. Hydrolysis of platelet-activating factor by human serum paraoxonase. Biochem. J. 354, 1\u2013 7 (2001).","journal-title":"Biochem. J."},{"key":"BFnsmb767_CR7","doi-asserted-by":"publisher","first-page":"24473","DOI":"10.1074\/jbc.M010459200","volume":"276","author":"Z Ahmed","year":"2001","unstructured":"Ahmed, Z. et al. Apolipoprotein A-I promotes the formation of phosphatidylcholine core aldehydes that are hydrolyzed by paraoxonase (PON-1) during high density lipoprotein oxidation with a peroxynitrite donor. J. Biol. Chem. 276, 24473\u2013 24481 (2001).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb767_CR8","doi-asserted-by":"publisher","first-page":"3957","DOI":"10.1074\/jbc.275.6.3957","volume":"275","author":"H Jakubowski","year":"2000","unstructured":"Jakubowski, H. Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J. Biol. Chem. 275, 3957\u2013 3962 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb767_CR9","doi-asserted-by":"publisher","first-page":"D1044","DOI":"10.2741\/1077","volume":"8","author":"S Lund-Katz","year":"2003","unstructured":"Lund-Katz, S., Liu, L.J., Thuahnai, S.T. & Phillips, M.C. High density lipoprotein structure. Front. Biosci. 8, D1044\u2013 D1054 (2003).","journal-title":"Front. Biosci."},{"key":"BFnsmb767_CR10","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0021-9150(01)00646-3","volume":"161","author":"B Fuhrman","year":"2002","unstructured":"Fuhrman, B., Volkova, N. & Aviram, M. Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase. Atherosclerosis 161, 307\u2013 316 (2002).","journal-title":"Atherosclerosis"},{"key":"BFnsmb767_CR11","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1161\/01.ATV.0000060462.35946.B3","volume":"23","author":"O Rozenberg","year":"2003","unstructured":"Rozenberg, O., Shih, D.M. & Aviram, M. Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: possible role for its phospholipase-A(2)-like activity and lysophosphatidylcholine formation. Arterioscler. Thromb. Vasc. Biol. 23, 461\u2013 467 (2003).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnsmb767_CR12","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1161\/01.ATV.19.9.2214","volume":"19","author":"RC Sorenson","year":"1999","unstructured":"Sorenson, R.C. et al. Human serum paraoxonase\/arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity. Arterioscler. Thromb. Vasc. Biol. 19, 2214\u2013 2225 (1999).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnsmb767_CR13","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1073\/pnas.2536901100","volume":"101","author":"A Aharoni","year":"2004","unstructured":"Aharoni, A. et al. Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization. Proc. Natl. Acad. Sci. USA 101, 482\u2013 487 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb767_CR14","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1107\/S0907444903017682","volume":"59","author":"A Fokine","year":"2003","unstructured":"Fokine, A. et al. Direct phasing at low resolution of a protein copurified with human paraoxonase (PON1). Acta Crystallogr. D. 59, 2083\u2013 2087 (2003).","journal-title":"Acta Crystallogr. D."},{"key":"BFnsmb767_CR15","doi-asserted-by":"publisher","first-page":"33386","DOI":"10.1074\/jbc.M200108200","volume":"277","author":"D Josse","year":"2002","unstructured":"Josse, D. et al. Oligomeric states of the detergent-solubilized human serum paraoxonase (PON1). J. Biol. Chem. 277, 33386\u2013 33397 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb767_CR16","first-page":"935","volume":"23","author":"CL Kuo","year":"1995","unstructured":"Kuo, C.L. & La Du, B.N. Comparison of purified human and rabbit serum paraoxonases. Drug Metab. Dispos. 23, 935\u2013 944 (1995).","journal-title":"Drug Metab. Dispos."},{"key":"BFnsmb767_CR17","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S0969-2126(02)00750-5","volume":"10","author":"Z Jawad","year":"2002","unstructured":"Jawad, Z. & Paoli, M. Novel sequences propel familiar folds. Structure 10, 447\u2013 454 (2002).","journal-title":"Structure"},{"key":"BFnsmb767_CR18","first-page":"653","volume":"26","author":"CL Kuo","year":"1998","unstructured":"Kuo, C.L. & La Du, B.N. Calcium binding by human and rabbit serum paraoxonases. Structural stability and enzymatic activity. Drug Metab. Dispos. 26, 653\u2013 60 (1998).","journal-title":"Drug Metab. Dispos."},{"key":"BFnsmb767_CR19","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0969-2126(01)00610-4","volume":"9","author":"EI Scharff","year":"2001","unstructured":"Scharff, E.I., Koepke, J., Fritzsch, G., Lucke, C. & Ruterjans, H. Crystal structure of diisopropylfluorophosphatase from Loligo vulgaris . Structure 9, 493\u2013 502 (2001).","journal-title":"Structure"},{"key":"BFnsmb767_CR20","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1021\/bi982281h","volume":"38","author":"D Josse","year":"1999","unstructured":"Josse, D. et al. Identification of residues essential for human paraoxonase (PON1) arylesterase\/organophosphatase activities. Biochemistry 38, 2816\u2013 2825 (1999).","journal-title":"Biochemistry"},{"key":"BFnsmb767_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S1388-1981(00)00153-0","volume":"1529","author":"A Jonas","year":"2000","unstructured":"Jonas, A. Lecithin cholesterol acyltransferase. Biochim. Biophys. Acta 1529, 245\u2013 256 (2000).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnsmb767_CR22","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1002\/jat.789","volume":"21","author":"D Josse","year":"2001","unstructured":"Josse, D. et al. The active site of human paraoxonase (PON1). J. Appl. Toxicol. 21, S7\u2013 S11 (2001).","journal-title":"J. Appl. Toxicol."},{"key":"BFnsmb767_CR23","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/S0009-2797(99)00016-2","volume":"120","author":"D Josse","year":"1999","unstructured":"Josse, D., Xie, W.H., Masson, P., Schopfer, L.M. & Lockridge, O. Tryptophan residue(s) as major components of the human serum paraoxonase active site. Chem. Biol. Interact. 120, 79\u2013 84 (1999).","journal-title":"Chem. Biol. Interact."},{"key":"BFnsmb767_CR24","doi-asserted-by":"publisher","first-page":"3104","DOI":"10.1021\/bi961576x","volume":"36","author":"K Sekar","year":"1997","unstructured":"Sekar, K. et al. Phospholipase A2 engineering. Structural and functional roles of the highly conserved active site residue aspartate-99. Biochemistry 36, 3104\u2013 3114 (1997).","journal-title":"Biochemistry"},{"key":"BFnsmb767_CR25","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1161\/01.ATV.18.10.1617","volume":"18","author":"M Aviram","year":"1998","unstructured":"Aviram, M. et al. Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase\/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler. Thromb. Vasc. Biol. 18, 1617\u2013 1624 (1998).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFnsmb767_CR26","doi-asserted-by":"publisher","first-page":"12787","DOI":"10.1073\/pnas.95.22.12787","volume":"95","author":"M Kobayashi","year":"1998","unstructured":"Kobayashi, M., Shinohara, M., Sakoh, C., Kataoka, M. & Shimizu, S. Lactone-ring-cleaving enzyme: genetic analysis, novel RNA editing, and evolutionary implications. Proc. Natl. Acad. Sci. USA 95, 12787\u2013 12792 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb767_CR27","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nature01205","volume":"420","author":"DS Chelur","year":"2002","unstructured":"Chelur, D.S. et al. The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel. Nature 420, 669\u2013 73 (2002).","journal-title":"Nature"},{"key":"BFnsmb767_CR28","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1097\/00041433-199810000-00009","volume":"9","author":"M Navab","year":"1998","unstructured":"Navab, M. et al. High density associated enzymes: their role in vascular biology. Curr. Opin. Lipidol. 9, 449\u2013 456 (1998).","journal-title":"Curr. Opin. Lipidol."},{"key":"BFnsmb767_CR29","doi-asserted-by":"publisher","first-page":"12291","DOI":"10.1073\/pnas.94.23.12291","volume":"94","author":"DW Borhani","year":"1997","unstructured":"Borhani, D.W., Rogers, D.P., Engler, J.A. & Brouillette, C.G. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation. Proc. Natl. Acad. Sci. USA 94, 12291\u2013 12296 (1997).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb767_CR30","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S1050-1738(00)00078-5","volume":"10","author":"JP Segrest","year":"2000","unstructured":"Segrest, J.P., Harvey, S.C. & Zannis, V. Detailed molecular model of apolipoprotein A-I on the surface of high-density lipoproteins and its functional implications. Trends Cardiovasc. Med. 10, 246\u2013 252 (2000).","journal-title":"Trends Cardiovasc. Med."},{"key":"BFnsmb767_CR31","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S0968-0004(00)01626-1","volume":"25","author":"JA Killian","year":"2000","unstructured":"Killian, J.A. & von Heijne, G. How proteins adapt to a membrane-water interface. Trends Biochem. Sci. 25, 429\u2013 434 (2000).","journal-title":"Trends Biochem. Sci."},{"key":"BFnsmb767_CR32","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S1367-5931(02)00017-0","volume":"7","author":"GS Waldo","year":"2003","unstructured":"Waldo, G.S. Genetic screens and directed evolution for protein solubility. Curr. Opin. Chem. Biol. 7, 33\u2013 38 (2003).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"BFnsmb767_CR33","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nsb919","volume":"10","author":"S Bencharit","year":"2003","unstructured":"Bencharit, S., Morton, C.L., Xue, Y., Potter, P.M. & Redinbo, M.R. Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat. Struct. Biol. 10, 349\u2013 356 (2003).","journal-title":"Nat. Struct. Biol."},{"key":"BFnsmb767_CR34","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1021\/bi972057c","volume":"37","author":"CB Millard","year":"1998","unstructured":"Millard, C.B., Lockridge, O. & Broomfield, C.A. Organophosphorus acid anhydride hydrolase activity in human butyrylcholinesterase: synergy results in a somanase. Biochemistry 37, 237\u2013 247 (1998).","journal-title":"Biochemistry"},{"key":"BFnsmb767_CR35","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1385\/JMN:20:3:369","volume":"20","author":"HM Greenblatt","year":"2003","unstructured":"Greenblatt, H.M., Dvir, H., Silman, I. & Sussman, J.L. Acetylcholinesterase: a multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease. J. Mol. Neurosci. 20, 369\u2013 383 (2003).","journal-title":"J. Mol. Neurosci."},{"key":"BFnsmb767_CR36","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S0022-2275(20)31161-5","volume":"42","author":"I Leviev","year":"2001","unstructured":"Leviev, I., Deakin, S. & James, R.W. Decreased stability of the M54 isoform of paraoxonase as a contributory factor to variations in human serum paraoxonase concentrations. J. Lipid Res. 42, 528\u2013 535 (2001).","journal-title":"J. Lipid Res."},{"key":"BFnsmb767_CR37","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1021\/bi001922h","volume":"40","author":"MN Oda","year":"2001","unstructured":"Oda, M.N., Bielicki, J.K., Berger, T. & Forte, T.M. Cysteine substitutions in apolipoprotein A-I primary structure modulate paraoxonase activity. Biochemistry 40, 1710\u2013 1718 (2001).","journal-title":"Biochemistry"},{"key":"BFnsmb767_CR38","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/0022-2836(71)90324-X","volume":"55","author":"B Lee","year":"1971","unstructured":"Lee, B. & Richards, F.M. The interpretation of protein structures: estimation of static accessibility. J. Mol. Biol. 55, 379\u2013 389 (1971).","journal-title":"J. Mol. Biol."}],"updated-by":[{"DOI":"10.1038\/nsmb1204-1253a","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000}}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nsmb767.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb767","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb767.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:53:01Z","timestamp":1684457581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nsmb767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,18]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,5,1]]}},"alternative-id":["BFnsmb767"],"URL":"https:\/\/doi.org\/10.1038\/nsmb767","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4,18]]},"assertion":[{"value":"23 February 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2004","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2004","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}