Showing papers on "Proteolytic enzymes published in 1981"
TL;DR: Fibrinogen is a soluble plasma protein that is converted to polymeric fibrin in response to damage to the vascular system as discussed by the authors, which forms the matrix of the tangle of cellular and molecular substances called the blood clot.
Abstract: Fibrinogen is a soluble plasma protein that is converted to polymeric fibrin in response to damage to the vascular system. The clotting process is initiated when platelets aggregate at the wound site. Their disruption releases biologically active amines and a proteolytic cascade follows which culminates in the conversion of fibrinogen to fibrin. The fibrin polymer forms the matrix of the tangle of cellular and molecular substances called the blood clot. Atomic-level details are now in hand for many of the interactions that hold fibrin units together, although some aspects have yet to be resolved. Of necessity, fibrin clots need to be dismantled when they are no longer needed, an operation largely accomplished by the proteolytic enzyme plasmin. Various regulatory phenomena are involved in maintaining the balance between intravascular fluidity and clots that prevent blood loss. A variety of hereditary conditions, including mutant fibrinogens, can predispose individuals to either thrombosis or bleeding.
Key concepts:
The underlying fabric of blood clots is a protein polymer called fibrin.
Fibrin clots are formed in response to injuries to any part of the vascular system.
The conversion of soluble fibrinogen molecules to insoluble fibrin depends on thrombin generated from prothrombin.
Keywords:
fibrinogen;
fibrin;
clot stabilisation;
fibrinolysis;
blood clotting;
X-ray structures
597 citations
TL;DR: It is concluded that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.
Abstract: To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (α-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (>80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P<0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in α-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients ...
515 citations
TL;DR: The complete amino acid sequence of hen ovalbumin, comprising 385 residues, has been determined from the 17 cyanogen bromide fragments and from peptides derived by digestion with a number of proteolytic enzymes.
Abstract: The complete amino acid sequence of hen ovalbumin, comprising 385 residues, has been determined. The sequence was deduced from the 17 cyanogen bromide fragments and from peptides derived by digestion with a number of proteolytic enzymes. The molecular weight of the polypeptide chain of ovalbumin is 42699. Ovalbumin has four sites of postsynthetic modification; in addition to the acetylated N terminus, the carbohydrate moiety is located at Asn-292, and the two phosphorylated serines are at residues 68 and 344. The 'signal sequence' of ovalbumin is between residues 234 and 252. The heptapeptide released during the conversion of ovalbumin to plakalbumin by subtilisin digestion corresponds to residues 346-352. The hen ovalbumin polymorphism characterised by an Asn leads to Asp replacement results from a mutation at residue 311. The amino acid sequence of ovalbumin deduced from these amino acid sequence studies is in complete agreement with the sequence of mRNA determined by McReynolds et al. [Nature (Lond.) 273, 723-728 (1978)].
454 citations
TL;DR: The polypeptide compositions of single- shelled and double-shelled simian rotavirus particles were modified by exposure to proteolytic enzymes, and the role of cleavage activation in other virus-specific biological functions (e.g., hemagglutination and virulence).
Abstract: The polypeptide compositions of single-shelled and double-shelled simian rotavirus particles were modified by exposure to proteolytic enzymes. Specifically, a major outer capsid polypeptide (VP3) having a molecular weight of 88,000 in double-shelled particles was cleaved by trypsin to yield two polypeptides, VP5* and VP8* (molecular weights, 60,000 and 28,000, respectively). The cleavage of VP3 by enzymes that enhanced infectivity (trypsin, elastase, and pancreatin) yielded different products compared to those detected when VP3 was cleaved by chymotrypsin, which did not enhance infectivity. The appearance of VP5* was correlated with an enhancement of infectivity. Cleavages of the major internal capsid polypeptide VP2 were also observed. The VP2 cleavage products had molecular weights similar to those of known structural and nonstructural rotavirus polypeptides. We confirmed the precursor-product relationships by comparing the peptide maps of the polypeptides generated by digestions with V-8 protease and chymotrypsin. The remaining rotavirus structural polypeptides, including the outer capsid glycoproteins (VP7 and 7a), were not altered by exposure to pancreatic enzymes. Cleavage of VP3 was not required for virus assembly, and specific cleavage of the polypeptides occurred only on assembled particles. We also discuss the role of cleavage activation in other virus-specific biological functions (e.g., hemagglutination and virulence).
366 citations
TL;DR: Data indicate that a unique receptor capable of interacting specifically with apo-E-containing lipoproteins, and not with apO-B-containinglipoprotein (LDL), exists in the adult canine liver.
364 citations
TL;DR: The adult cuticle of the soil nematode, Caenorhabditis elegans, is a proteinaceous extracellular structure elaborated by the underlying layer of hypodermal cells during the final molt in the animal's life cycle.
Abstract: The adult cuticle of the soil nematode, Caenorhabditis elegans, is a proteinaceous extracellular structure elaborated by the underlying layer of hypodermal cells during the final molt in the animal's life cycle. The cuticle is composed of an outer cortical layer connected by regularly arranged struts to an inner basal layer. The cuticle can be isolated largely intact and free of all cellular material by sonication and treatment with 1% sodium dodecyl sulfate (SDS). Purified cuticles exhibit a negative material in the basal cuticle layer. The cuticle layers differ in their solubility in sulfhydryl reducing agents, susceptibility to various proteolytic enzymes and amino acid composition. The struts, basal layer, and internal cortical layer are composed of collagen proteins that are extensively cross-linked by disulfide bonds. The external cortical layer appears to contain primarily noncollagen proteins that are extensively cross-linked by nonreducible covalent bonds. The collagen proteins extracted from the cuticle with a reducing agent can be separated by SDS-polyacrylamide gel electrophoresis into eight major species differing in apparent molecular weight.
349 citations
TL;DR: Type I procollagen was thermally denatured and partially refolded by cooling to 20°C and a mixture of chymotrypsin and trypsin was employed as an appropriate proteolytic probe for triple-helical conformation.
322 citations
TL;DR: The recognition that both the selectivity of many proteases and their catalytic efficiency depend on interactions with subsite amino acids in the peptide substrate coupled with the availability of amino acid sequences around the cleavage sites in several zymogens of the coagulation and fibrinolytic systems has led to the synthesis and commercial availability of a variety of peptide chromogenic and fluorogenic substrates with much greater selectivity.
Abstract: Publisher Summary Amino acid chromogenic and fluorogenic substrates have been used for many years for assaying proteases. The sensitivity of the assay procedures that employ these substrates and the convenience of spectrophotometric or fluorometric measurements has led to their widespread use. Most of the early amino acid chromogenic and fluorogenic substrates are highly selective for the primary specificity-determining (P1) amino acid; thus substrates such as benzoylarginine-p-nitroanilide, for assaying trypsin-like proteases, as well as aromatic amino acidp-nitrophenyl esters for chymotrypsin-like proteases, have been extensively investigated and employed for routine proteolytic enzyme assay. The recognition that both the selectivity of many proteases and their catalytic efficiency depend on interactions with subsite amino acids in the peptide substrate coupled with the availability of amino acid sequences around the cleavage sites in several zymogens of the coagulation and fibrinolytic systems has led to the synthesis and commercial availability of a variety of peptide chromogenic and fluorogenic substrates with much greater selectivity than the single amino acid chromogenic and fluorogenic substrates.
317 citations
TL;DR: The striking finding in their muscle biopsies was the presence of "rimmed" vacuoles which had acid phosphatase-positive autophagic activity and which contained numerous concentric lamellar bodies in various forms (myeloid and cabbage bodies).
255 citations
TL;DR: Bile acid salts were found to be less irritative to the nasal mucosa than non-ionic ether type surfactants and to be more inhibitory on proteolytic enzymes.
248 citations
TL;DR: Evidence is provided that the 40 kd protein is a keratin, and is neither a breakdown product nor an incomplete translation product of a gene for one of the larger keratins, and it is the smallest epidermal keratin yet to be described.
TL;DR: It is reported here that highly oriented fibrin gels are formed when polymerization takes place slowly in a strong magnetic field and it is shown that the protofibrils pack into a three-dimensional crystalline lattice.
Abstract: Fibrinogen is a soluble plasma protein which, after cleavage by the specific proteolytic enzyme thrombin, polymerizes to form the filamentous fibrin network during blood clotting (see refs 1 and 2 for reviews). Fibrinogen has a molecular weight of 340,000 and is composed of two identical halves, each containing three peptide chains designated A alpha, B beta and gamma. Fibrin monomers are produced by thrombin which releases the small negatively charged fibrinopeptides A and B. The overall shape of the fibrinogen molecule has not been unequivocally established. The trinodular, elongated (approximately 450 A long) structure proposed by Hall and Slayter is the most widely accepted model and it has obtained additional support from recent work. Fibrin monomers are also about 450 A long and in fibres they probably have a half-staggered arrangement along the axis. The fibres are an assembly of protofibrils whose structure and packing are not reliably known. We report here that highly oriented fibrin gels are formed when polymerization takes place slowly in a strong magnetic field. It is shown that the protofibrils pack into a three-dimensional crystalline lattice. We introduce magnetically induced birefringence as a potential tool for studying polymerization and briefly speculate on the applications of strong magnetic fields.
TL;DR: Fibrinolytic use of acylated derivatives of plasmin (E.C.4.7) and streptokinase–plasmin(ogen) complexes are reported here and it is reported that these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application.
Abstract: Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase–human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases1, with a catalytic mechanism which operates via acyl-enzyme intermediates2. Chase and Shaw3 showed that p-nitrophenyl-p′-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described4,5. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase–plasmin(ogen) complexes.
TL;DR: Human platelets incubated with a-chymotrypsin or pronase aggregated with fibrinogen even in the absence of platelet-activating compounds and showed enhanced agglutination with concanavalin A or Lens culinaris lectin, suggesting that the fibrInogen-induced platelet aggregation depends on the occupancy of high affinity fibr inogen receptors.
TL;DR: Achromobacter lyticus M497-1 produces three kinds of alkaline proteases (protease I, II and III) in culture medium along with the bacteriolytic enzyme, which shows strict splitting for lysine residues at the carboxyl side of the splitting point.
Journal Article•
TL;DR: Thyroglobulin antibodies failed to stain viable thyroid monolayers, indicating that this protein or possible receptors for it cannot be detected on the cell surface under these conditions, and some thyrotoxicosis sera containing thyroid-stimulating but not microsomal antibodies, gave negative reactions on viable cultures.
Abstract: The presence of organ-specific cell surface-reactive antibodies in sera of patients with autoimmune thyroid diseases (ATD) has been detected by indirect immunofluorescence on viable blood group O normal thyroid cultures The cell surface determinants involved in this reaction have been identified as the thyroid 'microsomal' antigen which is thus also represented on the outer surface of the plasma membrane The reactivity persists when F(ab')2 fragments from positive sera are used Non-thyroid cells present in the monolayers, as well as human adrenal or fibroblast cultures, do not show positive staining Human thyroid cells progressively lose both cell surface and intracytoplasmic antigenic components during the first week of culture The exposure and reactivity of this antigen on the cell surface do not depend upon unmasking effects of proteolytic enzymes used for dispersal of the cells The 'microsomal' antigen on the cell surface is also involved in the complement-mediated cytotoxic effect of sera from ATD patients on freshly dispersed thyroid cells Thyroglobulin antibodies failed to stain viable thyroid monolayers, even when these were previously incubated with purified human thyroglobulin, indicating that this protein or possible receptors for it cannot be detected on the cell surface under these conditions Similarly, some thyrotoxicosis sera containing thyroid-stimulating but not microsomal antibodies, gave negative reactions on viable cultures
TL;DR: The studies demonstrate the existence of eight distinct soluble proteolytic activities in E. coli, and one of the globin-degrading enzymes is stimulated markedly by ATP and thus may be the rate-limiting enzyme for protein breakdown in vivo.
Abstract: Escherichia coli selectively degrades polypeptides with highly abnormal conformations1–4. Normal cell proteins are degraded more slowly, but this process increases when the bacteria lack required nutrients1,5–7. The pathways by which aberrant or normal proteins are hydrolysed are not known1,3,4, but these processes require metabolic energy3–5,8,9. Recently, cell-free proteolytic systems have been obtained from E. coli4,10 and mammalian cells3,11–15 that are stimulated by ATP. To clarify the pathway of intracellular protein degradation and to determine whether ATP might directly influence specific proteolytic enzymes, we have now undertaken to define the various proteases in E. coli. Our studies demonstrate the existence of eight distinct soluble proteolytic activities in E. coli extracts. Seven seem to be new enzymes. Six are serine proteases that hydrolyse 14C-globin and 3H-casein, while two others are metalloenzymes that degrade 125I-insulin but not these larger polypeptides. One of the globin-degrading enzymes is stimulated markedly by ATP and thus may be the rate-limiting enzyme for protein breakdown in vivo.
TL;DR: The relationship between proteolysis and off-flavor development in ultra-high temperature and pasteurized milk was investigated in this paper, where raw, pasteurized and ultra high temperature milk were subjected to proteolytic enzymes for 20h at 35°C.
TL;DR: It is suggested that once the mitochondrial cholesterol side-chain cleavage system is fully activated by ACTH, the supply of cholesterol to the mitochondria becomes rate-limiting for steroidogenesis, and sufficient cholesterol is obtained to provide for precursor cholesterol to maintain the high rate of steroid synthesis by the HFA.
Abstract: A model proposed for regulation of steroidogenesis, lipoprotein utilization and cholesterol metabolism in HFA tissue is presented in Fig 17. We envision that the role of ACTH and cAMP in steroidogenesis and cholesterol metabolism is as follows. ACTH binds to specific receptors on the surface of the cells of the HFA gland and as a consequence, adenylate cyclase is activated, leading to increased formation of cAMP. cAMP causes activation of protein kinase that leads, presumably, to phosphorylation of specific proteins. This leads to the initiation of reactions that give rise to increased activity of key enzymes and levels of proteins involved in adrenal cholesterol metabolism. Presumably, the action of ACTH causes an increase in the activity of cholesterol side chain cleavage, the rate-limiting step in the conversion of cholesterol to steroid hormones. We suggest that once the mitochondrial cholesterol side-chain cleavage system is fully activated by ACTH, the supply of cholesterol to the mitochondria becomes rate-limiting for steroidogenesis. To meet this demand for cholesterol, a further action of ACTH results in an increase in the number of LDL receptors. LDL binds to specific receptors on the cell surface that are localized in coated pits. LDL is internalized by a process of adsorptive endocytosis and the internalized vesicles fuse with lysosomes and the protein component of LDL is hydrolyzed by lysosomal proteolytic enzymes to amino acids. The cholesteryl esters of LDL also are hydrolyzed to give rise to fatty acids and cholesterol. The liberated cholesterol is available for utilization in the biosynthesis of steroid hormones and other cellular processes. In addition, ACTH stimulates the activity of HMG CoA reductase and, thus, the rate of de novo cholesterol biosynthesis. In this way sufficient cholesterol is obtained to provide for precursor cholesterol to maintain the high rate of steroid synthesis by the HFA. HDL is not utilized as a source of cholesterol by the HFA. Because of the rapid rate of utilization of LDL by the HFA, fetal plasma levels of LDL are low and the activity of the HFA is a primary determinant of these levels. Thus, in the case of anencephaly, in which the activity of the adrenal is very low, plasma levels of LDL are 2--3 times higher than in normal fetuses, whereas plasma HDL levels are similar. In addition, in the normal neonate plasma LDL levels rise rapidly after birth, and this event is coincident with the involution of the fetal zone of the adrenal. The fetal liver is likely to be the major source ultimately of the LDL-cholesterol utilized by the HFA. Consequently, factors that regulate cholesterol and lipoprotein synthesis in the fetal liver may, in turn, affect the steroidogenic activity of the HFA through regulation of the supply of cholesterol precursor. Thus, if trophic factors for the HFA other than ACTH exist, an important site of their action might be the fetal liver, rather than a direct action to influence the rate of synthesis of steroids by the fetal adrenal.
TL;DR: After the binding of IgG to the surface Fc receptor of Schistosoma mansoni schistosomula, the Fab portions of IgGs are cleaved and small peptides are liberated in the culture medium.
Abstract: After the binding of IgG to the surface Fc receptor of Schistosoma mansoni schistosomula, the Fab portions of IgG are cleaved and small peptides are liberated in the culture medium. At least two types of proteinase activities have been demonstrated in the secretory products of schistosomula. One is an endoprotease with trypsin-like activity, with an optimum pH of 7 and an optimum temperature of 45 degrees C. The other is a metalloaminopeptidase with an optimum pH of 7 and temperature of 37 degrees C.
01 Jan 1981
TL;DR: This chapter discusses physicochemical properties of lectins in higher plants, including their ability to form precipitates with polysaccharides or glycoproteins, either in liquid or semisolid media and their interactions provide information regarding lectin specificity.
Abstract: Publisher Summary This chapter discusses physicochemical properties of lectins in higher plants. Lectins are best defined as sugar-binding and cell-agglutinating proteins of nonimmune origin. In contrast to antibodies, which are structurally similar, lectins vary in composition, MW, subunit structure, and number of sugar-binding sites. The presence of a lectin in a plant is readily detected by testing whether an extract of the plant agglutinates erythrocytes and by demonstrating that the agglutination is sugar-specific. Blood group-specific lectins are identified with the aid of a panel of typed human erythrocytes. The most common cell modification is mild digestion with trypsin or other proteolytic enzymes or with neuraminidase, an enzyme that removes sialic acid from complex carbohydrates. Lectins may also be detected by their ability to form precipitates with polysaccharides or glycoproteins, either in liquid or semisolid media. Such interactions also provide information regarding lectin specificity, and on the constituent sugars and glycosidic linkages of the polysaccharide or glycoprotein precipitated.
TL;DR: Findings strongly suggest that the intracellular uncoating of reovirus to the level of active transcriptase proceeds via a pathway which is mechanistically identical to that elucidated for un coating and transcriptase activation in vitro.
TL;DR: MuCANP is produced from mCANP only by the specific autolysis of mCANp, and muCANP did not yield muCAN p from m CANP at lower Ca2+ concentrations where only muCANp was active.
Abstract: The conditions and process of autolysis of calcium-activated neutral protease (CANP) were examined. Optimal conditions for autolysis were the same as those required for expression of activity of CANP. The autolysis proceeded rapidly by a strictly limited proteolysis. During autolysis the molecular weight of CANP changed from 82 K (native CANP or mCANP) to 79 K and then 60 K. The 79 K and 60 K molecular species were both active at microM order of Ca2+ (muCANP), whereas the native CANP is active at mM order of Ca2+ (mCANP). Various proteases examined did not produce muCANP from mcanp under the conditions tested. Furthermore, muCANP did not yield muCANP from mCANP at lower Ca2+ concentrations where only muCANP was active. Therefore, muCANP is produced from mCANP only by the specific autolysis of mCANP.
TL;DR: The unique specificity of Achromobacter protease I for lysine residue was investigated using synthetic and natural substrates and the binding affinity of alkylamines as determined by Ki was much stronger than that of the corresponding alkylguanidines.
TL;DR: Proteolytic enzymes seem to be “reabsorbed” in the hindgut of the fish and the effectiveness of this mechanism rises up to a relative gut length of 2.5–3.0, but the small species Amblypharyngodon melletinus does not fit this relationship.
Abstract: Proteolytic activity in the gut contents of two cichlids and six cyprinids from an artificial basin in Sri Lanka was measured using a simple film strip method. This comparative study contributes to our general knowledge of digestion in herbivorous fish: 1) Specific proteolytic activity (per ml of gut content) is lower in herbivorous than in omnivorous and carnivorous species. 2) Specific proteolytic activity is negatively correlated with the relative length of the gut, but the time of exposure of ingested food to proteolytic enzymes rises with increasing gut length. This results in more intensive proteolytic digestion in herbivorous fish. 3) Proteolytic enzymes seem to be "reabsorbed" in the hindgut of the fish. The effectiveness of this mechanism rises up to a relative gut length of 2.5-3.0. However, the small species Amblypharyngodon melletinus does not fit this relationship.
TL;DR: Observations are consistent with a mechanism for iron uptake into hepatocytes involving the binding of iron‐transferrin to a specific cell‐surface receptor.
TL;DR: The cytosol of human erythrocytes was found to contain a Ca2+-dependent thiol protease (calpain) and its specific inhibitor (calpastatin) by DEAE-cellulose chromatography at pH 8.0, although no proteolytic activity toward casein was detected in the unfractionated hemolysate.
Abstract: The cytosol of human erythrocytes was found to contain a Ca2+-dependent thiol protease (calpain) and its specific inhibitor (calpastatin) by DEAE-cellulose chromatography at pH 8.0, although no proteolytic activity toward casein was detected in the unfractionated hemolysate. The protease required only 40 microM Ca2+ for 50% activation, indicating that it belongs to the highly Ca2+-sensitive type of calpain, namely, calpain I. It was not inactivated by heating at 58 degrees C for 10 min at pH 7.2, the optimal pH for its action on casein. The inhibitor comprised major and minor components, calpastatin H (Mr = 280,000) and caplastatin L (Mr = 48,000). Both were heat-stable proteins which were readily inactivated by tryptic digestion. The inhibition of erythrocyte calpain by erythrocyte calpastatin H or L was not due to sequestering of Ca2+ from the reaction medium by the inhibitor protein. The calpain preparation preferentially digests bands III and IVa of human erythrocyte membrane proteins, with little or no cleavage of the bands corresponding to spectrin.
TL;DR: The results indicate that the biosynthesis of calcitonin involves the glycosylation and proteolytic cleavage of a newly synthesized precursor along with sequestration of the processed precursor within microsomal vesicles to form the smaller, unglycosylated hormone that is secreted.
TL;DR: These molecules provide probes for many sites on the acetylcholine receptor with affinities and specificities comparable to alpha-neurotoxins.
Abstract: The isolated subunits of the acetylocholine receptor from Torpedo californica were digested with proteolytic enzymes, and the resulting polypeptide fragments were analyzed by gel electrophoresis We have identified those fragments which contain carbohydrate and those from the alpha subunit which are labelled with the acetylcholine binding site specific reagent [4-(N-maleimido)benzyl]tri[3H]methylammonium iodide We have tested several monoclonal antibodies raised to the acetylcholine receptor from torpedo, some of which react with the denatured subunits [Tzartos, SJ, & Lindstrom, JM (1980) Proc Natl Acad Sci USA77, 755; Tzartos, SJ, & Lindstrom, JM (1981) in Monoclonal antibodies in Endocrine Research (Fellows, R, & Eisenbarth, G, Eds) Raven Press (in press)] The binding specificities of these antibodies to radioiodinated proteolytically generated fragments of the alpha subunit were determined by immunoprecipitation followed by gel electrophoresis The antibodies tested fell into at least three main groups on the basis of their binding specificities These antibodies were also tested for their capacity to bind to acetylcholine receptor solubilized in Triton X-100, sodium cholate, or sodium cholate supplemented with exogenous lipids A monoclonal antibody raised to the denatured delta subunit, was tested for its ability to select radioiodinated proteolytic fragments of these subunits These molecules provide probes for many sites on the acetylcholine receptor with affinities and specificities comparable to alpha-neurotoxins