{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:54:06Z","timestamp":1760853246132},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4900","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1989,4,7]]},"abstract":"<jats:p>\n            Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A\n            <jats:sub>2<\/jats:sub>\n            does not change the binding constant for micelles significantly, but it improves catalytic activity up to 16 times on micellar (zwitterionic) lecithin substrates. In contrast, the decrease in activity on negatively charged substrates is greater than fourfold. A crystallographic study of the mutant enzyme shows that the region of the deletion has a well-defined structure that differs from the structure of the wild-type enzyme. No structural changes in the active site of the enzyme were detected.\n          <\/jats:p>","DOI":"10.1126\/science.2704992","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T21:21:28Z","timestamp":1160083288000},"page":"82-85","source":"Crossref","is-referenced-by-count":78,"title":["Enhanced Activity and Altered Specificity of Phospholipase A\n            <sub>2<\/sub>\n            by Deletion of a Surface Loop"],"prefix":"10.1126","volume":"244","author":[{"given":"Oscar P.","family":"Kuipers","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Utrecht, Center for Biomembranes and Lipid Energy, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolein M. G. M.","family":"Thunnissen","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, University of Groninge, Groninge, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"de Geus","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Utrecht, Center for Biomembranes and Lipid Energy, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bauke W.","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, University of Groninge, Groninge, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Drenth","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, University of Groninge, Groninge, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubertus M.","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Utrecht, Center for Biomembranes and Lipid Energy, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard H.","family":"de Haas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Utrecht, Center for Biomembranes and Lipid Energy, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"9742","DOI":"10.1016\/S0021-9258(17)39301-8","volume":"260","year":"1985","unstructured":"BRUNIE, S, THE REFINED CRYSTAL-STRUCTURE OF DIMERIC PHOSPHOLIPASE-A2 AT 2.5 A - ACCESS TO A SHIELDED CATALYTIC CENTER, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 9742 (1985).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1093\/nar\/13.12.4431","volume":"13","year":"1985","unstructured":"CARTER, P, IMPROVED OLIGONUCLEOTIDE SITE-DIRECTED MUTAGENESIS USING M13 VECTORS, NUCLEIC ACIDS RESEARCH 13: 4431 (1985).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1107\/S0365110X67003172","volume":"23","year":"1967","unstructured":"CROWTHER, R.A., A METHOD OF POSITIONING A KNOWN MOLECULE IN AN UNKNOWN CRYSTAL STRUCTURE, ACTA CRYSTALLOGRAPHICA 23: 544 (1967).","journal-title":"ACTA CRYSTALLOGRAPHICA"},{"key":"e_1_2_1_4_1","first-page":"173","year":"1972","unstructured":"Crowther, R. A., The Molecular Replacement Method: 173 (1972).","journal-title":"The Molecular Replacement Method"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1093\/nar\/15.9.3743","volume":"15","year":"1987","unstructured":"DEGEUS, P, EXPRESSION OF PORCINE PANCREATIC PHOSPHOLIPASE-A2 - GENERATION OF ACTIVE ENZYME BY SEQUENCE-SPECIFIC CLEAVAGE OF A HYBRID PROTEIN FROM ESCHERICHIA-COLI, NUCLEIC ACIDS RESEARCH 15: 3743 (1987).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_6_1","unstructured":"de Haas G. H. Biochemical Journal in press."},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1107\/S0567740882004099","volume":"38","year":"1982","unstructured":"DIJKSTRA, B.W., THE STRUCTURE OF BOVINE PANCREATIC PROPHOSPHOLIPASE A2 AT 3.0 A RESOLUTION, ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE 38: 793 (1982).","journal-title":"ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1021\/bi00307a035","volume":"23","year":"1984","unstructured":"DIJKSTRA, B.W., ROLE OF THE N-TERMINUS IN THE INTERACTION OF PANCREATIC PHOSPHOLIPASE-A2 WITH AGGREGATED SUBSTRATES - PROPERTIES AND CRYSTAL-STRUCTURE OF TRANSAMINATED PHOSPHOLIPASE-A2, BIOCHEMISTRY 23: 2759 (1984).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0022-2836(81)90081-4","volume":"147","year":"1981","unstructured":"DIJKSTRA, B.W., STRUCTURE OF BOVINE PANCREATIC PHOSPHOLIPASE-A2 AT 1.7A RESOLUTION, JOURNAL OF MOLECULAR BIOLOGY 147: 97 (1981).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0022-2836(83)80328-3","volume":"168","year":"1983","unstructured":"DIJKSTRA, B.W., STRUCTURE OF PORCINE PANCREATIC PHOSPHOLIPASE-A2 AT 2.6-A RESOLUTION AND COMPARISON WITH BOVINE PHOSPHOLIPASE-A2, JOURNAL OF MOLECULAR BIOLOGY 168: 163 (1983).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/289604a0","volume":"289","year":"1981","unstructured":"DIJKSTRA, B.W., ACTIVE-SITE AND CATALYTIC MECHANISM OF PHOSPHOLIPASE-A2, NATURE 289: 604 (1981).","journal-title":"NATURE"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"8381","DOI":"10.1021\/bi00374a008","volume":"25","year":"1986","unstructured":"FORST, S, STRUCTURAL AND FUNCTIONAL-PROPERTIES OF A PHOSPHOLIPASE-A2 PURIFIED FROM AN INFLAMMATORY EXUDATE, BIOCHEMISTRY 25: 8381 (1986).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1107\/S0021889887086102","volume":"20","year":"1987","unstructured":"FUJINAGA, M, EXPERIENCES WITH A NEW TRANSLATION-FUNCTION PROGRAM, JOURNAL OF APPLIED CRYSTALLOGRAPHY 20: 517 (1987).","journal-title":"JOURNAL OF APPLIED CRYSTALLOGRAPHY"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1021\/cr00081a010","volume":"87","year":"1987","unstructured":"GERLT, J.A., RELATIONSHIPS BETWEEN ENZYMATIC CATALYSIS AND ACTIVE-SITE STRUCTURE REVEALED BY APPLICATIONS OF SITE-DIRECTED MUTAGENESIS, CHEMICAL REVIEWS 87: 1079 (1987).","journal-title":"CHEMICAL REVIEWS"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/oxfordjournals.jbchem.a121996","volume":"101","year":"1987","unstructured":"HAYAKAWA, M, AMINO-ACID-COMPOSITION AND NH2-TERMINAL AMINO-ACID-SEQUENCE OF RAT PLATELET SECRETORY PHOSPHOLIPASE-A2, JOURNAL OF BIOCHEMISTRY 101: 1311 (1987).","journal-title":"JOURNAL OF BIOCHEMISTRY"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/oxfordjournals.jbchem.a122547","volume":"104","year":"1988","unstructured":"HAYAKAWA, M, THE PRIMARY STRUCTURE OF RAT PLATELET PHOSPHOLIPASE-A2, JOURNAL OF BIOCHEMISTRY 104: 767 (1988).","journal-title":"JOURNAL OF BIOCHEMISTRY"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/bip.360220136","volume":"22","year":"1983","unstructured":"HUBER, R, FUNCTIONAL-SIGNIFICANCE OF FLEXIBILITY IN PROTEINS, BIOPOLYMERS 22: 261 (1983).","journal-title":"BIOPOLYMERS"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0076-6879(85)15014-7","volume":"115","year":"1985","unstructured":"JONES, T.A., INTERACTIVE COMPUTER-GRAPHICS - FRODO, METHODS IN ENZYMOLOGY 115: 157 (1985).","journal-title":"METHODS IN ENZYMOLOGY"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"9441","DOI":"10.1093\/nar\/12.24.9441","volume":"12","year":"1984","unstructured":"KRAMER, W, THE GAPPED DUPLEX DNA APPROACH TO OLIGONUCLEOTIDE-DIRECTED MUTATION CONSTRUCTION, NUCLEIC ACIDS RESEARCH 12: 9441 (1984).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.1016\/S0021-9258(18)60626-X","volume":"263","year":"1988","unstructured":"ONO, T, PURIFICATION AND CHARACTERIZATION OF A MEMBRANE-ASSOCIATED PHOSPHOLIPASE-A2 FROM RAT SPLEEN - ITS COMPARISON WITH A CYTOSOLIC PHOSPHOLIPASE-A2 S-1, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 5732 (1988).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_21_1","first-page":"1627","volume":"260","year":"1985","unstructured":"RENETSEDER, R, A COMPARISON OF THE CRYSTAL-STRUCTURES OF PHOSPHOLIPASE-A2 FROM BOVINE PANCREAS AND CROTALUS-ATROX VENOM, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 1627 (1985).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_22_1","first-page":"194","volume":"8","year":"1988","unstructured":"RIPKA, W.C., ICSU SHORT REPORT 8: 194 (1988).","journal-title":"ICSU SHORT REPORT"},{"key":"e_1_2_1_23_1","first-page":"95","volume":"9","year":"1987","unstructured":"RIPKA, W.C., LECTURES HETEROCYCLI 9: 95 (1987).","journal-title":"LECTURES HETEROCYCLI"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1107\/S0108767387099124","volume":"43","year":"1987","unstructured":"TRONRUD, D.E., AN EFFICIENT GENERAL-PURPOSE LEAST-SQUARES REFINEMENT PROGRAM FOR MACROMOLECULAR STRUCTURES, ACTA CRYSTALLOGRAPHICA SECTION A 43: 489 (1987).","journal-title":"ACTA CRYSTALLOGRAPHICA SECTION A"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/0006-3002(63)90792-3","volume":"70","year":"1963","unstructured":"VANDEENEN, LLM, SUBSTRATE SPECIFICITY OF PHOSPHOLIPASE A, BIOCHIMICA ET BIOPHYSICA ACTA 70: 538 (1963).","journal-title":"BIOCHIMICA ET BIOPHYSICA ACTA"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1432-1033.1983.tb07345.x","volume":"132","year":"1983","unstructured":"VANEIJK, J.H., INTERACTION OF PHOSPHOLIPASE-A2 FROM NAJA-MELANOLEUCA SNAKE-VENOM WITH MONOMERIC SUBSTRATE-ANALOGS - ACTIVATION OF THE ENZYME BY PROTEIN-PROTEIN OR LIPID-PROTEIN INTERACTIONS, EUROPEAN JOURNAL OF BIOCHEMISTRY 132: 183 (1983).","journal-title":"EUROPEAN JOURNAL OF BIOCHEMISTRY"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"7987","DOI":"10.1021\/bi00348a022","volume":"24","year":"1985","unstructured":"VANOORT, M.G., KINETIC-BEHAVIOR OF PORCINE PANCREATIC PHOSPHOLIPASE-A2 ON ZWITTERIONIC AND NEGATIVELY CHARGED SINGLE-CHAIN SUBSTRATES, BIOCHEMISTRY 24: 7987 (1985).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1021\/bi00504a016","volume":"20","year":"1981","unstructured":"VERHEIJ, H.M., CHEMICAL MODIFICATION OF THE ALPHA-AMINO GROUP IN SNAKE-VENOM PHOSPHOLIPASES-A2 - A COMPARISON OF THE INTERACTION OF PANCREATIC AND VENOM PHOSPHOLIPASES WITH LIPID-WATER INTERFACES, BIOCHEMISTRY 20: 94 (1981).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_29_1","first-page":"69","volume":"1","year":"1982","unstructured":"Volwerk, J. J., Lipid-Protein Interactions 1: 69 (1982).","journal-title":"Lipid-Protein Interactions"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/recl.19790980414","volume":"98","year":"1979","unstructured":"VOLWERK, J. J., RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS-JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY 98: 214 (1979).","journal-title":"RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS-JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY"},{"key":"e_1_2_1_31_1","unstructured":"Waite M. Handbook of Lipid Research 5 (1987)."},{"key":"e_1_2_1_32_1","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1021\/bi00708a002","volume":"13","year":"1974","unstructured":"WELLS, M.A., MECHANISM OF INTERFACIAL ACTIVATION OF PHOSPHOLIPASE A2, BIOCHEMISTRY 13: 2248 (1974).","journal-title":"BIOCHEMISTRY"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.2704992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T22:29:46Z","timestamp":1705098586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.2704992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,4,7]]},"references-count":32,"journal-issue":{"issue":"4900","published-print":{"date-parts":[[1989,4,7]]}},"alternative-id":["10.1126\/science.2704992"],"URL":"https:\/\/doi.org\/10.1126\/science.2704992","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,4,7]]}}}