{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:31:46Z","timestamp":1781105506450,"version":"3.54.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,25]]},"abstract":"<jats:p>Pigment epithelium-derived factor (PEDF), a noninhibitory member of\n the serpin superfamily, is the most potent inhibitor of angiogenesis in\n the mammalian ocular compartment. It also has neurotrophic activity,\n both in the retina and in the central nervous system, and is highly\n up-regulated in young versus senescent fibroblasts. To provide a\n structural basis for understanding its many biological roles, we have\n solved the crystal structure of glycosylated human PEDF to 2.85 \u212b. The\n structure revealed the organization of possible receptor and\n heparin-binding sites, and showed that, unlike any other previously\n characterized serpin, PEDF has a striking asymmetric charge\n distribution that might be of functional importance. These results\n provide a starting point for future detailed structure\/function\n analyses into possible mechanisms of PEDF action that could lead to\n development of therapeutics against uncontrolled angiogenesis.<\/jats:p>","DOI":"10.1073\/pnas.211268598","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"11131-11135","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor"],"prefix":"10.1073","volume":"98","author":[{"given":"Miljan","family":"Simonovic","sequence":"first","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology, and\r Microbiology and Immunology, College of Medicine,\r University of Illinois, Chicago, IL 60612-7334"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G. W.","family":"Gettins","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology, and\r Microbiology and Immunology, College of Medicine,\r University of Illinois, Chicago, IL 60612-7334"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Volz","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology, and\r Microbiology and Immunology, College of Medicine,\r University of Illinois, Chicago, IL 60612-7334"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,9,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0014-4835(91)90248-D","volume":"53","author":"Tombran-Tink J","year":"1991","unstructured":"J Tombran-Tink, G G Chader, L V Johnson Exp Eye Res 53, 411\u2013414 (1991).","journal-title":"Exp Eye Res"},{"key":"e_1_3_4_2_2","first-page":"2759","volume":"37","author":"Ortego J","year":"1996","unstructured":"J Ortego, J Escribano, S P Becerra, M Coca-Prados Invest Ophthalmol Vis Sci 37, 2759\u20132767 (1996).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_3_2","first-page":"1984","volume":"37","author":"Wu Y Q","year":"1996","unstructured":"Y Q Wu, S P Becerra Invest Ophthalmol Vis Sci 37, 1984\u20131993 (1996).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_4_2","first-page":"11","volume":"2","author":"Tombran-Tink J","year":"1996","unstructured":"J Tombran-Tink, K Mazuruk, I Rodriguez, D Chung, T Linker, E Englander, G Chader Mol Vis 2, 11\u201319 (1996).","journal-title":"Mol Vis"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"25992","DOI":"10.1074\/jbc.270.43.25992","volume":"270","author":"Becerra S P","year":"1995","unstructured":"S P Becerra, A Sagasti, P Spinella, V Notario J Biol Chem 270, 25992\u201325999 (1995).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_6_2","first-page":"1700","volume":"30","author":"Tombran-Tink J","year":"1989","unstructured":"J Tombran-Tink, L Johnson Invest Ophthalmol Visl Sci 30, 1700\u20131709 (1989).","journal-title":"Invest Ophthalmol Visl Sci"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/1097-4644(20001201)79:3<442::AID-JCB90>3.0.CO;2-Z","volume":"79","author":"Coljee V W","year":"2000","unstructured":"V W Coljee, M O Rotenberg, M Tresini, M K Francis, V J Cristofalo, C Sell J Cell Biochem 79, 442\u2013452 (2000).","journal-title":"J Cell Biochem"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"8949","DOI":"10.1016\/S0021-9258(18)52964-1","volume":"268","author":"Pignolo R J","year":"1993","unstructured":"R J Pignolo, V J Cristofalo, M O Rotenberg J Biol Chem 268, 8949\u20138957 (1993).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1523\/JNEUROSCI.15-07-04992.1995","volume":"15","author":"Tombran-Tink J","year":"1995","unstructured":"J Tombran-Tink, S M Shivaram, G J Chader, L V Johnson, D Bok J Neurosci 15, 4992\u20135003 (1995).","journal-title":"J Neurosci"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3109\/08977199409010995","volume":"10","author":"Seigel G M","year":"1994","unstructured":"G M Seigel, J Tombran-Tink, S P Becerra, G J Chader, D A Diloreto, C del Cerro, E S Lazar, M del Cerro Growth Factors 10, 289\u2013297 (1994).","journal-title":"Growth Factors"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1046\/j.1471-4159.1995.64062509.x","volume":"64","author":"Taniwaki T","year":"1995","unstructured":"T Taniwaki, S P Becerra, G J Chader, J P Schwartz J Neurochem 64, 2509\u20132517 (1995).","journal-title":"J Neurochem"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/(SICI)1096-9861(19990927)412:3<506::AID-CNE9>3.0.CO;2-E","volume":"412","author":"Houenou L J","year":"1999","unstructured":"L J Houenou, A P D'Costa, L Li, V L Turgeon, C Enyadike, E Alberdi, S P Becerra J Comp Neurol 412, 506\u2013514 (1999).","journal-title":"J Comp Neurol"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1046\/j.1471-4159.1997.68010026.x","volume":"68","author":"Taniwaki T","year":"1997","unstructured":"T Taniwaki, N Hirashima, S P Becerra, G J Chader, R Etcheberrigaray, J P Schwartz J Neurochem 68, 26\u201332 (1997).","journal-title":"J Neurochem"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/00005072-199907000-00006","volume":"58","author":"Bilak M M","year":"1999","unstructured":"M M Bilak, A M Corse, S R Bilak, M Lehar, J Tombran-Tink, R W Kuncl J Neuropathol Exp Neurol 58, 719\u2013728 (1999).","journal-title":"J Neuropathol Exp Neurol"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/(SICI)1097-4547(19990615)56:6<604::AID-JNR6>3.0.CO;2-B","volume":"56","author":"DeCoster M A","year":"1999","unstructured":"M A DeCoster, E Schabelman, J Tombran-Tink, N G Bazan J Neurosci Res 56, 604\u2013610 (1999).","journal-title":"J Neurosci Res"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/(SICI)1097-4547(19990915)57:6<789::AID-JNR4>3.0.CO;2-M","volume":"57","author":"Cao W","year":"1999","unstructured":"W Cao, J Tombran-Tink, W Chen, D Mrazek, R Elias, J F McGinnis J Neurosci Res 57, 789\u2013800 (1999).","journal-title":"J Neurosci Res"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1006\/nbdi.1999.0263","volume":"6","author":"Cayouette M","year":"1999","unstructured":"M Cayouette, S B Smith, S P Becerra, C Gravel Neurobiol Dis 6, 523\u2013532 (1999).","journal-title":"Neurobiol Dis"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"7149","DOI":"10.1523\/JNEUROSCI.20-19-07149.2000","volume":"20","author":"Jablonski M M","year":"2000","unstructured":"M M Jablonski, J Tombran-Tink, D A Mrazek, A Iannaccone J Neurosci 20, 7149\u20137157 (2000).","journal-title":"J Neurosci"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/(SICI)1097-4547(19970915)49:6<710::AID-JNR5>3.0.CO;2-A","volume":"49","author":"Sugita Y","year":"1997","unstructured":"Y Sugita, S P Becerra, G J Chader, J P Schwartz J Neurosci Res 49, 710\u2013718 (1997).","journal-title":"J Neurosci Res"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.285.5425.245","volume":"285","author":"Dawson D W","year":"1999","unstructured":"D W Dawson, O V Volpert, P Gillis, S E Crawford, H Xu, W Benedict, N P Bouck Science 285, 245\u2013248 (1999).","journal-title":"Science"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1073\/pnas.061024098","volume":"98","author":"Chader G J","year":"2001","unstructured":"G J Chader Proc Natl Acad Sci USA 98, 2122\u20132124 (2001).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1073\/pnas.031252398","volume":"98","author":"Stellmach V","year":"2001","unstructured":"V Stellmach, S E Crawford, W Zhou, N Bouck Proc Natl Acad Sci USA 98, 2593\u20132597, . (First Published January 23, 2001; 10.1073\/pnas.031252398). (2001).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_23_2","volume-title":"Retina","author":"Schachat A","year":"1994","unstructured":"A Schachat, R Murphy Retina (Mosby, Baltimore, 1994)."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-3076-2","volume-title":"Corneal Angiogenesis: A Comprehensive Critical Review","author":"Klintworth G","year":"1991","unstructured":"G Klintworth Corneal Angiogenesis: A Comprehensive Critical Review (Springer, New York, 1991)."},{"key":"e_1_3_4_25_2","first-page":"222","volume":"34","author":"Kaminska G","year":"1993","unstructured":"G Kaminska, J Niederkorn Invest Ophthalmol Vis Sci 34, 222\u2013230 (1993).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"10643","DOI":"10.1021\/bi9802317","volume":"37","author":"Alberdi E","year":"1998","unstructured":"E Alberdi, C C Hyde, S P Becerra Biochemistry 37, 10643\u201310652 (1998).","journal-title":"Biochemistry"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"31605","DOI":"10.1074\/jbc.274.44.31605","volume":"274","author":"Alberdi E","year":"1999","unstructured":"E Alberdi, M S Aymerich, S P Becerra J Biol Chem 274, 31605\u201331612 (1999).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1002\/pro.5560051220","volume":"5","author":"Stratikos E","year":"1996","unstructured":"E Stratikos, E Alberdi, P G Gettins, S P Becerra Protein Sci 5, 2575\u20132582 (1996).","journal-title":"Protein Sci"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1107\/S0021889891004430","volume":"24","author":"Jancarik J","year":"1991","unstructured":"J Jancarik, S H Kim J App Crystallogr 24, 409\u2013411 (1991).","journal-title":"J App Crystallogr"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0076-6879(97)76072-5","volume":"276","author":"Otwinowski Z","year":"1997","unstructured":"Z Otwinowski, W Minor Methods Enzymol 276, 461\u2013472 (1997).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1107\/S0907444998003254","volume":"54","author":"Br\u00fcnger A","year":"1998","unstructured":"A Br\u00fcnger Acta Crystallogr D 54, 905\u2013921 (1998).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_32_2","volume-title":"quanta","year":"1997","unstructured":"quanta (San Diego, 1997)."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1107\/S0021889891004399","volume":"24","author":"Kraulis P J","year":"1991","unstructured":"P J Kraulis J Appl Crystallogr 24, 946\u2013950 (1991).","journal-title":"J Appl Crystallogr"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1021\/bi00449a001","volume":"28","author":"Huber R","year":"1989","unstructured":"R Huber, R Carrell Biochemistry 28, 8951\u20138966 (1989).","journal-title":"Biochemistry"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/prot.340110407","volume":"11","author":"Nicholls A","year":"1991","unstructured":"A Nicholls, K Sharp, B Honig Proteins 11, 281\u2013296 (1991).","journal-title":"Proteins"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"10881","DOI":"10.1093\/nar\/16.22.10881","volume":"16","author":"Corpet F","year":"1988","unstructured":"F Corpet Nucleic Acids Res 16, 10881\u201310890 (1988).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1073\/pnas.96.9.4808","volume":"96","author":"Stratikos E","year":"1999","unstructured":"E Stratikos, P Gettins Proc Natl Acad Sci USA 96, 4808\u20134813 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_38_2","volume-title":"Serpins: Structure, Function and Biology","author":"Gettins P G W","year":"1996","unstructured":"P G W Gettins, P A Patston, T A Olson Serpins: Structure, Function and Biology (Landes, Austin, TX, 1996)."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"5432","DOI":"10.1021\/bi9702142","volume":"36","author":"Huntington J A","year":"1997","unstructured":"J A Huntington, B Fan, K E Karlsson, J Deinum, D A Lawrence, P G Gettins Biochemistry 36, 5432\u20135440 (1997).","journal-title":"Biochemistry"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.211268598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T01:28:37Z","timestamp":1654565317000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.211268598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,18]]},"references-count":39,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2001,9,25]]}},"alternative-id":["10.1073\/pnas.211268598"],"URL":"https:\/\/doi.org\/10.1073\/pnas.211268598","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,18]]},"assertion":[{"value":"2001-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-09-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}