Primary structure of γ-bungarotoxin, a new postsynaptic neurotoxin from venom of Bungarus multicinctus

被引:32
作者
Aird, SD
Womble, GC
Yates, JR
Griffin, PR
机构
[1] NPS Pharmaceut, Salt Lake City, UT 84108 USA
[2] CALTECH, Div Biol, Pasadena, CA 91125 USA
关键词
snake venom; postsynaptic neurotoxin; hydrophobicity; toxicity; primary structure; disulfide bond positions;
D O I
10.1016/S0041-0101(98)00199-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The primary structure of gamma-bungarotoxin, a new toxin from Bungarus multicinctus venom, was determined using mass spectrometry and Edman degradation. The toxin has a mass of 7524.7 D and consists of 68 residues having the following sequence: MQCKTCSFYT CPNSETCPDG KNICVKRSWT AVRGDGPKRE IRRECAATCP PSKLGLTVFC CTTDNCNH. gamma-bungarotoxin is structurally similar to both kappa-bungarotoxin and elapid long postsynaptic neurotoxins. Its C-terminal nine residues are identical to those of the kappa-toxins. Its disulfide bond locations appear identical to those of several elapid toxins of unknown pharmacology and its hydrophobicity profile is also strikingly similar. However, with an LD50 of 0.15 mu g/g i.v. in mice, gamma-bungarotoxin is 30-150-fold more toxic than other members of this latter class. Its toxicity is comparable to those of alpha-nicotinic acetylcholine receptor antagonists. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:609 / 625
页数:17
相关论文
共 42 条
[1]   TOXICITY ASSAYS [J].
AIRD, SD ;
KAISER, II .
TOXICON, 1985, 23 (01) :11-13
[2]   PRIMARY SEQUENCES AND NEUROMUSCULAR EFFECTS OF 3 NEUROTOXIC POLYPEPTIDES FROM VENOM OF DENDROASPIS-VIRIDIS [J].
BANKS, BEC ;
MILEDI, R ;
SHIPOLINI, RA .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1974, 45 (02) :457-468
[3]  
BECHIS G, 1976, EUR J BIOCHEM, V68, P445, DOI 10.1111/j.1432-1033.1976.tb10832.x
[4]  
BOTES DP, 1971, J BIOL CHEM, V246, P7383
[5]   SNAKE-VENOM TOXINS PRIMARY STRUCTURE OF PROTEIN S4C11 - NEUROTOXIN HOMOLOGUE FROM VENOM OF FOREST COBRA (NAJA-MELANOLEUCA) [J].
CARLSSON, FHH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1975, 400 (02) :310-321
[6]  
Chang LS, 1997, BIOCHEM MOL BIOL INT, V43, P347
[7]   KAPPA-NEUROTOXINS - HETERODIMER FORMATION BETWEEN DIFFERENT NEURONAL NICOTINIC RECEPTOR ANTAGONISTS [J].
CHIAPPINELLI, VA ;
WOLF, KM .
BIOCHEMISTRY, 1989, 28 (21) :8543-8547
[8]   KAPPA-FLAVITOXIN - ISOLATION OF A NEW NEURONAL NICOTINIC RECEPTOR ANTAGONIST THAT IS STRUCTURALLY RELATED TO KAPPA-BUNGAROTOXIN [J].
CHIAPPINELLI, VA ;
WOLF, KM ;
DEBIN, JA ;
HOLT, IL .
BRAIN RESEARCH, 1987, 402 (01) :21-29
[9]   Binding of native kappa-neurotoxins and site-directed mutants to nicotinic acetylcholine receptors [J].
Chiappinelli, VA ;
Weaver, WR ;
McLane, KE ;
ContiFine, BM ;
Fiordalisi, JJ ;
Grant, GA .
TOXICON, 1996, 34 (11-12) :1243-1256
[10]  
CHIAPPINELLI VA, 1985, J BIOL CHEM, V260, P6182