{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:48:51Z","timestamp":1789516131347,"version":"build-2803163510"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5187","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1994,11,11]]},"abstract":"<jats:p>\n            The venom of the funnel-web spider\n            <jats:italic>Agelenopsis aperta<\/jats:italic>\n            contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, \u03c9-Aga-IVB (IVB) and \u03c9-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in\n            <jats:italic>A. aperta<\/jats:italic>\n            venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.\n          <\/jats:p>","DOI":"10.1126\/science.7973665","type":"journal-article","created":{"date-parts":[[2006,10,6]],"date-time":"2006-10-06T00:01:25Z","timestamp":1160092885000},"page":"1065-1068","source":"Crossref","is-referenced-by-count":135,"title":["Functional Consequences of Posttranslational Isomerization of Ser\n            <sup>46<\/sup>\n            in a Calcium Channel Toxin"],"prefix":"10.1126","volume":"266","author":[{"given":"Steven D.","family":"Heck","sequence":"first","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chester J.","family":"Siok","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen J.","family":"Krapcho","sequence":"additional","affiliation":[{"name":"NPS Pharmaceuticals Incorporated, Salt Lake City, Utah 84108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Kelbaugh","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Thadeio","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Welch","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan H.","family":"Ganong","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Lanzetti","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Gray","sequence":"additional","affiliation":[{"name":"Departments of Biology and Anatomy, University of Utah, Salt Lake City, Utah 84112, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Phillips","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas N.","family":"Parks","sequence":"additional","affiliation":[{"name":"Departments of Biology and Anatomy, University of Utah, Salt Lake City, Utah 84112, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Jackson","sequence":"additional","affiliation":[{"name":"NPS Pharmaceuticals Incorporated, Salt Lake City, Utah 84108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Ahlijanian","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Saccomano","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Volkmann","sequence":"additional","affiliation":[{"name":"Pfizer Research Incorporated, Groton, CT 06340, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","unstructured":"Phillips D. U.S. patent 5 122 596 (1992).","DOI":"10.2307\/1395291"},{"key":"e_1_2_1_2_1","first-page":"681","volume":"44","year":"1993","unstructured":"ADAMS, M.E., STRUCTURE AND PROPERTIES OF OMEGA-AGATOXIN-IVB, A NEW ANTAGONIST OF P-TYPE CALCIUM CHANNELS, MOLECULAR PHARMACOLOGY 44: 681 (1993).","journal-title":"MOLECULAR PHARMACOLOGY"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev.ph.51.030189.002055","volume":"51","year":"1989","unstructured":"BEAN, B.P., CLASSES OF CALCIUM CHANNELS IN VERTEBRATE CELLS, ANNUAL REVIEW OF PHYSIOLOGY 51: 367 (1989).","journal-title":"ANNUAL REVIEW OF PHYSIOLOGY"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/365496a0","volume":"365","year":"1993","unstructured":"BRANTON, W.D., FATTY ACYLATED TOXIN STRUCTURE, NATURE 365: 496 (1993).","journal-title":"NATURE"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_1_6_1","first-page":"5058","volume":"89","year":"1992","unstructured":"DUBEL, S.J., MOLECULAR-CLONING OF THE ALPHA-1 SUBUNIT OF AN OMEGA-CONOTOXIN-SENSITIVE CALCIUM-CHANNEL, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 5058 (1992).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/363455a0","volume":"363","year":"1993","unstructured":"ELLINOR, P.T., FUNCTIONAL EXPRESSION OF A RAPIDLY INACTIVATING NEURONAL CALCIUM-CHANNEL, NATURE 363: 455 (1993).","journal-title":"NATURE"},{"key":"e_1_2_1_8_1","first-page":"61","volume":"85","year":"1986","unstructured":"FORD, R, COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY 85: 61 (1986).","journal-title":"COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY"},{"key":"e_1_2_1_9_1","first-page":"8998","volume":"85","year":"1988","unstructured":"FROHMAN, M.A., RAPID PRODUCTION OF FULL-LENGTH CDNAS FROM RARE TRANSCRIPTS - AMPLIFICATION USING A SINGLE GENE-SPECIFIC OLIGONUCLEOTIDE PRIMER, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 8998 (1988).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1021\/bi00066a019","volume":"32","year":"1993","unstructured":"GALLO, K.A., PURIFICATION, CLONING, AND COFACTOR INDEPENDENCE OF GLUTAMATE RACEMASE FROM LACTOBACILLUS, BIOCHEMISTRY 32: 3981 (1993).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1021\/bi00066a020","volume":"32","year":"1993","unstructured":"GALLO, K.A., MECHANISM OF THE REACTION CATALYZED BY GLUTAMATE RACEMASE, BIOCHEMISTRY 32: 3991 (1993).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_12_1","first-page":"7212","volume":"19","year":"1993","unstructured":"GANONG, A.H., SOC NEUR ABSTR 19: 7212 (1993).","journal-title":"SOC NEUR ABSTR"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0014-5793(94)80413-3","volume":"339","year":"1994","unstructured":"GRABNER, M, MOLECULAR-CLONING OF AN ALPHA(1)-SUBUNIT FROM HOUSEFLY (MUSCA-DOMESTICA) MUSCLE, FEBS LETTERS 339: 189 (1994).","journal-title":"FEBS LETTERS"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1021\/ja00102a009","volume":"116","year":"1994","unstructured":"Heck, S. D., Journal of the American Chemical Society 116: 10426 (1994).","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/cne.903030105","volume":"303","year":"1991","unstructured":"HORNBERG, U, J COMP NEUROL 303: 35 (1991).","journal-title":"J COMP NEUROL"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"10967","DOI":"10.1016\/S0021-9258(19)78075-2","volume":"269","year":"1994","unstructured":"KREIL, G, PEPTIDES CONTAINING A D-AMINO-ACID FROM FROGS AND MOLLUSKS, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 10967 (1994).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0965-1748(93)90068-4","volume":"23","year":"1993","unstructured":"LAMANGO, N.S., METABOLISM OF INSECT NEUROPEPTIDES - PROPERTIES OF A MEMBRANE-BOUND ENDOPEPTIDASE FROM HEADS OF MUSCA-DOMESTICA, INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY 23: 801 (1993).","journal-title":"INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY"},{"key":"e_1_2_1_18_1","first-page":"1689","volume":"86","year":"1989","unstructured":"LLINAS, R, BLOCKING AND ISOLATION OF A CALCIUM-CHANNEL FROM NEURONS IN MAMMALS AND CEPHALOPODS UTILIZING A TOXIN FRACTION (FTX) FROM FUNNEL-WEB SPIDER POISON, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 1689 (1989).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/355827a0"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90223-Z"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/350398a0","volume":"350","year":"1991","unstructured":"MORI, Y, PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION FROM COMPLEMENTARY-DNA OF A BRAIN CALCIUM-CHANNEL, NATURE 350: 398 (1991).","journal-title":"NATURE"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1126\/science.2165278","volume":"249","year":"1990","unstructured":"OLIVERA, B.M., DIVERSITY OF CONUS NEUROPEPTIDES, SCIENCE 249: 257 (1990).","journal-title":"SCIENCE"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0896-6273(91)90362-4","volume":"6","year":"1991","unstructured":"REGAN, L.J., CA2+ CHANNELS IN RAT CENTRAL AND PERIPHERAL NEURONS - HIGH-THRESHOLD CURRENT RESISTANT TO DIHYDROPYRIDINE BLOCKERS AND OMEGA-CONOTOXIN, NEURON 6: 269 (1991).","journal-title":"NEURON"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1126\/science.3659910","volume":"238","year":"1987","unstructured":"RICHTER, K, D-ALANINE IN THE FROG-SKIN PEPTIDE DERMORPHIN IS DERIVED FROM L-ALANINE IN THE PRECURSOR, SCIENCE 238: 200 (1987).","journal-title":"SCIENCE"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1021\/bi00691a028","volume":"14","year":"1975","unstructured":"RUDNICK, G, REACTION-MECHANISM AND STRUCTURE OF ACTIVE-SITE OF PROLINE RACEMASE, BIOCHEMISTRY 14: 4515 (1975).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90185-T"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0016-6480(88)90046-9","volume":"69","year":"1988","unstructured":"SCHOOFS, L, METHIONINE-ENKEPHALIN IMMUNOREACTIVITY IN THE GONADS AND NERVOUS-SYSTEM OF 2 INSECT SPECIES - LOCUSTA-MIGRATORIA AND SARCOPHAGA-BULLATA, GENERAL AND COMPARATIVE ENDOCRINOLOGY 69: 1 (1988).","journal-title":"GENERAL AND COMPARATIVE ENDOCRINOLOGY"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8388125"},{"key":"e_1_2_1_29_1","first-page":"363","volume":"44","year":"1992","unstructured":"SPEDDING, M, CLASSIFICATION OF CALCIUM CHANNELS AND THE SITES OF ACTION OF DRUGS MODIFYING CHANNEL FUNCTION, PHARMACOLOGICAL REVIEWS 44: 363 (1992).","journal-title":"PHARMACOLOGICAL REVIEWS"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.1021\/ja00359a014","volume":"105","year":"1983","unstructured":"TAM, J.P., SN2 DEPROTECTION OF SYNTHETIC PEPTIDES WITH A LOW CONCENTRATION OF HF IN DIMETHYL SULFIDE - EVIDENCE AND APPLICATION IN PEPTIDE-SYNTHESIS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 105: 6442 (1983).","journal-title":"JOURNAL OF THE AMERICAN CHEMICAL SOCIETY"},{"key":"e_1_2_1_31_1","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1021\/bi00066a021","volume":"32","year":"1993","unstructured":"TANNER, M.E., ISOTOPE EFFECTS AND THE IDENTIFICATION OF CATALYTIC RESIDUES IN THE REACTION CATALYZED BY GLUTAMATE RACEMASE, BIOCHEMISTRY 32: 3998 (1993).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_32_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1006\/bbrc.1993.2225","volume":"196","year":"1993","unstructured":"TERAMOTO, T, A NOVEL PEPTIDE FROM FUNNEL-WEB SPIDER VENOM, OMEGA-AGA-TK, SELECTIVELY BLOCKS P-TYPE CALCIUM CHANNELS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 196: 134 (1993).","journal-title":"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS"},{"key":"e_1_2_1_33_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0165-6147(91)90595-J","volume":"12","year":"1991","unstructured":"TSIEN, R.W., MOLECULAR DIVERSITY OF VOLTAGE-DEPENDENT CA2+ CHANNELS, TRENDS IN PHARMACOLOGICAL SCIENCES 12: 349 (1991).","journal-title":"TRENDS IN PHARMACOLOGICAL SCIENCES"},{"key":"e_1_2_1_34_1","first-page":"828","year":"1979","unstructured":"Walsh, C., Enzymatic Reaction Mechanisms: 828 (1979).","journal-title":"Enzymatic Reaction Mechanisms"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"22347","DOI":"10.1016\/S0021-9258(17)31796-9","volume":"269","year":"1994","unstructured":"WILLIAMS, M.E., STRUCTURE AND FUNCTIONAL-CHARACTERIZATION OF NEURONAL ALPHA(1E) CALCIUM-CHANNEL SUBTYPES, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 22347 (1994).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1321501"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","first-page":"18361","DOI":"10.1016\/S0021-9258(19)36969-8","volume":"267","year":"1992","unstructured":"YAMAUCHI, T, PROPERTIES OF ASPARTATE RACEMASE, A PYRIDOXAL 5'-PHOSPHATE-INDEPENDENT AMINO-ACID RACEMASE, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 18361 (1992).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_38_1","doi-asserted-by":"crossref","first-page":"13123","DOI":"10.1021\/bi00211a022","volume":"32","year":"1993","unstructured":"YU, H.T., SEQUENTIAL ASSIGNMENT AND STRUCTURE DETERMINATION OF SPIDER TOXIN OMEGA-AGA-IVB, BIOCHEMISTRY 32: 13123 (1993).","journal-title":"BIOCHEMISTRY"},{"key":"e_1_2_1_39_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/0028-3908(93)90003-L","volume":"32","year":"1993","unstructured":"ZHANG, J.F., DISTINCTIVE PHARMACOLOGY AND KINETICS OF CLONED NEURONAL CA2+ CHANNELS AND THEIR POSSIBLE COUNTERPARTS IN MAMMALIAN CNS NEURONS, NEUROPHARMACOLOGY 32: 1075 (1993).","journal-title":"NEUROPHARMACOLOGY"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.7973665","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:20:31Z","timestamp":1705292431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.7973665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11,11]]},"references-count":39,"journal-issue":{"issue":"5187","published-print":{"date-parts":[[1994,11,11]]}},"alternative-id":["10.1126\/science.7973665"],"URL":"https:\/\/doi.org\/10.1126\/science.7973665","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11,11]]}}}