아브린 C화학적 특성, 용도, 생산
용도
expertly in cancer research.
Safety Profile
A deadly poison to humans byingestion. Poison by ingestion, intravenous, andintraperitoneal routes. Mutation data reported. Whenheated to decomposition it emits acrid fumes and irritatingsmoke.
효소 저해제
This type-II ribosome-inactivating glycoprotein toxin (MW = 65 kDa; CAS 1393-62-0) from the seeds of Abrus precatorius (common names: rosary pea and jequirity) is composed of an acidic A chain and a neutral B chain joined by disulfide bonds. The A chain exhibits the toxic rRNA Nglycosidase activity, catalyzing the endohydrolysis of a specific Nglycosidic bond at an adenosine on rRNA, thereby irreversibly inactivating protein synthesis (See Ricin). The B chain has lectin-like properties that assist A chain entry into cells. Chewing jequirity seeds has proved fatal, because each molecule of abrin can inactivate as many as 1,500 ribosomes per second (~75x more active than ricin). Note: Abrin should not be confused with abrine, or Na-methyl-L-tryptophan. Mode of Apoptotic Action: The abrin A chain also promotes apoptosis, which is preceded by mitochondrial cytochrome c release, followed by caspase-3 and -9 activation. The broad-spectrum caspase inhibitor, benzyloxycarbonyl- Val-Ala-Asp-fluoromethyl ketone (zVADfmk), prevents abrin-triggered caspase activation and reduces apoptotic cell death, but is without effect on cytochrome c release. Such results suggest that the sequential caspase activation is crucial for abrin-induced apoptosis. Abrin also inhibits the mitochondrial antioxidant protein AOP-1. Recent studies suggest that abrin-induced apoptosis depends on p38 MAPK (but not JNK), attended by activation of caspase-2 and caspase-8, triggering Bid cleavage and and to subsequent mitochondrial membrane potential loss. Such a pathway connects the signaling events from ER stress to mitochondrial death machinery. Target(s): protein biosynthesis; ribosome; antioxidant protein AOP-1
Purification Methods
These are toxic lectins (proteins) from seeds of Abras precatorius. The yellow-white powder is purified by successive chromatography on DEAE-Sephadex A-50, carboxymethylcellulose, and DEAE-cellulose. Abrin A is more positively charged on the DEAE-cellulose column and has been crystallised from (NH4)2SO4 by the free interface diffusion technique. Its molecular weight (by sedimentation equilibrium) is 60,000, whereas Abrin C has molecular weight of 63,800. Treatment of A with mercaptoethanol at 100o/2hours followed by SDSPAGE gave a main band with Mr 32,000 and two very weak bands, whereas C (which is more toxic) gave two intense bands with Mr 28,000 and 33,000. [Wei et al. J Biol Chem 249 3061 1974.] Abrin C has been crystallised for X-ray analysis by the free interface diffusion technique described by Salemme [Arch Biochim Biophys 151 533 1972]. The crystals were grown at 37o in Pyrex tubes (5 x 30 cm) by layering 50l of protein solution (22mg/mL) over 100l of unbuffered 70% saturated (NH4)2SO4 [Wei & Einstein J Biol Chem 249 2985 1974.] [UV and CD: Herrmann & Behnke Biochem Biophys Acta 621 43 1980, for physical and chemical properties see Biochem Biophys Acta 667 397 1981, Beilstein 22 III/IV 6776.]
아브린 준비 용품 및 원자재
원자재
준비 용품
