Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiotoxin, isolated from Naja naja atra snake venom, potentiates platelet aggregation induced by ADP, thrombin, collagen and venom phospholipase A2. The malondialdehyde formation caused by ADP, thrombin and venom phospholipase A2 were also increased in the presence of cardiotoxin. Both potentiation of aggregation and increase in malondialdehyde were blocked by indomethacin or Ca2+ (5 mM or 0.05 mM). Cardiotoxin did not potentiate thrombin-induced aggregation of p-bromophenacyl bromide-modified platelets. Thromboxane B2 formation induced by thrombin or collagen was also increased by cardiotoxin, while that by arachidonate was not affected. As a membrane-active polypeptide, cardiotoxin might augment the Ca2+-flux during the activation of the platelet membrane by aggregation inducers and then increase the activation of endogenous phospholipase A2.
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PMID:Cardiotoxin from Naja naja atra snake venom: a potentiator of platelet aggregation. 647 95

beta-Bungarotoxin, which consists of two polypeptide chains (A- and B-chain), in the venom of Formosan banded krait is stable in 7.5 M urea but can be denatured in 6.0 M guanidine hydrochloride. Its conformation remains virtually the same in solvents of lower polarity than water such as a mixture of 1,2-ethanediol-water (4:1 by volume). The circular dichroism spectrum in water shows a double minima at 222 and 209 nm, which is characteristic of the helical structure. The ellipticities at these two wavelengths indicate that the helical content of this toxin is not high. Comparing how guanidine hydrochloride effects the helix-coil transition of the toxin with that of phospholipase A2's which are structurally homologous to A-chain implicates that the two polypeptide chains should be coexisted and interacted with each other in order to maintain the active conformation of beta-bungarotoxin. Removal of eight amino acid residues from the N-terminus of the A-chain by action of CNBr on beta-bungarotoxin does not disrupt the polypeptide folding but abolishes the neurotoxicity.
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PMID:Optical activity and conformation of beta-bungarotoxin in solution. 657 84

The Gila monster (genus Heloderma) is the only known lizard to produce and inject a venomous secretion. Little is known about the venom from these lizards, and none of the toxins have been isolated until this time. This paper reports the isolation and characterization of a major lethal toxin (gilatoxin) from the venoms of Heloderma suspectum and Heloderma horridum. Gilatoxins from both species were similar in amino acid composition, electrophoretic mobility, pI, and immunological reactivity. They are acidic proteins possessing molecular weights of 35 000-37 500 and isoelectric points of 4.25 and consist of a single polypeptide chain. Neither is antigenically related to the venoms of snakes. The toxins are devoid of phospholipase A2 activity and proteolytic, hemorrhagic, and hemolytic activities, with lethality being the only biological activity detectably expressed. The toxins appear to be unique and distinct from those of other venomous animals.
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PMID:Biochemical characterization of the lizard toxin gilatoxin. 678 71

Caudoxin, a single-chain phospholipase A2 isolated from the venom of Bitis caudalis is a toxic polypeptide with a formula weight of 13,332 dalton. The LD50 in mice (i.p.) was 0.18 (0.15-0.22) mg/kg. In the chick biventer cervicis muscle preparation the toxin (1-10 micrograms per ml) caused complete neuromuscular blockade without affecting the response of the muscle to acetylcholine. In the mouse phrenic nerve-diaphragm preparation, the toxin abolished the indirectly elicited contraction without inhibiting that evoked directly. When this preparation was bathed in a low calcium (0.6 mM) medium, the toxin induced a triphasic change in the indirectly evoked contractions: an immediate initial inhibition followed by augmentation and then a second phase of inhibition leading to irreversible neuromuscular blockade. Electrophysiological studies in the same preparation showed a similar triphasic change in the quantal content of endplate potentials. The frequency of miniature endplate potentials first increased and then decreased, while the resting membrane potential was not significantly decreased by the toxin. Histological study showed that the toxin caused local myonecrosis only at a higher dose (2 mg/kg mouse). It is concluded that caudoxin produced a neuromuscular block by acting selectively on a presynaptic site. However, the site of binding appears to be different from that of beta-bungarotoxin since combination of the toxin with beta-bungarotoxin caused potentiation of its neuromuscular blocking action rather than addition.
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PMID:Site of action of caudoxin, a neurotoxic phospholipase A2 from the horned puff adder (Bitis caudalis) venom. 710 10

Delta toxin, one of at least four toxins produced by pathogenic strains of the skin bacterium Staphylococcus aureus, is an amphipathic polypeptide possessing hemolytic and cytolytic activity. Delta toxin stimulates high levels of phospholipase A2 activity in 3T3 mouse fibroblasts with concomitant synthesis and release of prostaglandins. Alpha toxin, another hemolytic toxin produced by strains of S. aureus, did not stimulate phospholipase A2 or prostaglandin release in these cells. Analysis of the release of lactate dehydrogenase and beta-galactosidase (cytoplasmic and lysosomal marker enzymes, respectively) from delta-toxin-treated cells indicated that cytolytic concentrations of the toxin damage the cell-surface membrane more extensively than lysosomal membranes. During a 30 min exposure, delta toxin stimulated 3T3 cells to hydrolyze up to 32% of the lipids biosynthetically labeled by incorporation of [3H]arachidonic acid. A relatively high percentage of the free arachidonic acid formed in delta-toxin-treated 3T3 cells was converted to prostaglandins (up to 41.3% and 8.3% converted to chromatographically identifiable prostaglandins E2 and F2 alpha, respectively, in 30 min), with optimal conversion occurring at sublytic toxin concentrations. The degree of activation of phospholipase A2 in 3T3 cells by a range of concentrations of delta toxin correlates with cytotoxicity assessed by failure to exclude trypan blue dye. Analysis of the calcium dependency of the toxin-activated phospholipase A2 was consistent with a cell-surface, Ca2+-dependent enzyme. The phospholipase A2 exhibits a degree of specificity for substrate lipids containing polyunsaturated fatty acid residues which can serve as precursors for prostaglandin formation. Enzymatic activity was not inhibited by diisopropylfluorophosphate (5 mM), N-ethylmaleimide (5 mM) or p-bromophenacylbromide (0.1 mM). Delta toxin did not activate detectable phospholipase A2 in subcellular preparations containing plasma membrane.
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PMID:Staphylococcal delta toxin stimulates endogenous phospholipase A2 activity and prostaglandin synthesis in fibroblasts. 721 81

The involvement of lipids in the structure and the activity of the fatty acid synthetase from the insect Ceratitis capitata has been previously established. Lipid-protein interactions were examined by circular dichroism. A thermal transition for both the structure and the activity of the enzyme complex takes place at about 50 degrees C; as the temperature is raised alpha-helix content decreases considerably and, concomitantly, the enzyme undergoes a marked inactivation. After 180 min at 37 degrees C, the secondary structure of the enzyme complex is 20% alpha-helix, 33% beta structure and 47% of not ordered structure against 43%, 26% and 31% as respective percentages for the native form of the complex. Lipolytic digestion of the complex was carried out with either lipase or phospholipase A2 or a mixture of both enzymes. Any of the lipolytic treatments induces a decrease of [theta]220 and the simultaneous digestion with lipase plus phospholipase during 90 min account for a limit structure with 8% of alpha-helix. The secondary structure of the complex after treatment with proteolytic enzymes, trypsin or chymotrypsin, had 15% alpha-helix, 20% beta structure and 57% of not ordered structure. The preservation of the alpha-helix content indicates that lipids protect certain of the bonds cleavable in the absence of lipids. The structural organization of the complex was studied through sequences of lipolytic and proteolytic treatments; final organization was dependent on the initial lipolytic digestion in agreement with the peptide bond shielding by the lipid component. Nitration of the complex with tetranitromethane modified almost completely all tyrosine residues of the polypeptide chains.
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PMID:Fatty acid synthetase complex from the insect Ceratitis capitata. Structural studies. 722 10

A photolabile analogue of phosphatidylethanolamine (photolabile PE analogue), 1,2-di-O-hexylglycero-3-(ethyl diazomalonamidoethyl phosphate), was synthesized in nonisotopic and 14C-radiolabeled form and in both the L configuration (that of the naturally occurring phospholipids) and the racemic form. When the unlabeled racemic compound was photolyzed in the presence of phospholipase A2 of Crotalus atrox, extensive enzyme inactivation was observed. The rate of inactivation was stimulated by Ca2+ and by formation of micelles of the photolabile compound. The dihexyl ether analogue of phosphatidylethanolamine protected the enzyme from inactivation. Phospholipase A2 gave rise to a covalently labeled polypeptide when irradiated in the presence of either L or racemic 14C-labeled photolabile PE analogue. The racemic compound labeled both the N-terminal region (residues 1--15) and the central region (residues 43--97) of the polypeptide while the L compound labeled only the N-terminal region. The lone methionine at position 10 of the C. atrox phospholipase A2 permitted degradation by cyanogen bromide, which showed that labeling by the L compound was restricted to the first ten amino acid residues at the N-terminal end. Phospholipase A2 has an absolute specificity for L-phospholipids, and D-phospholipids are competitive inhibitors. The results of these studies underscore the importance of the head-group region of the phospholipid in phospholipase--substrate interactions and suggest that the two optical isomers of the substrate may be rather differently oriented on the enzyme surface.
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PMID:Photoaffinity labeling of Crotalus atrox phospholipase A2 by a substrate analogue. 747 Apr 71

Polymerase chain reaction (PCR) was employed to amplify cDNAs constructed from the poly(A)+RNA of venom glands in Taiwan cobras to facilitate the cloning and sequencing of phospholipase A2 (PLA2) gene. The PCR product was then subcloned into pUC18 vector and transformed in E. coli strain JM109. Plasmids purified from the positive clones were prepared for nucleotide sequencing by dideoxynucleotide chain-termination method. Sequencing several clones containing about 0.5 kb DNA inserts constructed a complete and unambiguous full-length reading frame of 468 base pairs covering a precursor for phospholipase A2 with a deduced mature protein sequence of 119 amino acids and a 27 amino-acid segment of signal peptide. The sequenced major PLA2 with pI 4.991 shows a high degree of sequence homology to those PLA2 of the same or closely-related genus. The deduced protein sequence allows us to correct and resolve some discrepancy between the sequences determined by conventional protein sequencing (Toxicon, 19, 141(1981)) and X-ray crystallography (Science, 250, 1560(1990)). Expression of PLA2 in E. coli vector generated a polypeptide which can cross-react with the antiserum against the native and purified PLA2 from the same cobra venom albeit with a much lower activity.
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PMID:Sequence analysis and expression of phospholipase A2 from Taiwan cobra. 751 Sep 63

The cDNA sequence encoding phospholipase A2 (PLA2) was determined by analysis of polymerase-chain-reaction (PCR) product amplified from total cDNA mixture which had been constructed from the poly(A)+RNA of venom glands obtained from Taiwan cobras. Two oligonucleotide segments corresponding to the 5'- and 3'-noncoding regions of sea-snake PLA2 gene were used as primers for PCR-amplified reaction. Plasmids of transformed E. coli strain JM109 containing amplified PLA2 cDNA were purified and prepared for nucleotide sequencing by dideoxynucleotide chain-termination method. Sequencing more than five clones containing about 0.5 kb DNA inserts revealed two isoforms with complete reading frames of 468 base pairs each covering a precursor for phospholipase A2 with a deduced mature protein sequence of 119 amino acids and a 27 amino-acid signal peptide. These two enzymes of Group I PLA2 differ in six nucleotide residues at the gene level and three amino acids along the whole polypeptide chain, each consisting of 14 cysteine residues similar to all reported PLA2 of different snake venoms. The signal peptides and hydropathy profiles of Group I PLA2 reported here are distinctly different from those of Group II PLA2 in viperid snakes.
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PMID:cDNA and protein sequences coding for the precursor of phospholipase A2 from Taiwan cobra, Naja naja atra. 752 2

The intrinsic polypeptide D1, isolated from photosystem (PS) II-particles of the cyanobacterium Oscillatoria chalybea, was obtained by electroelution and fractionated extraction with organic solvents. Purification was demonstrated by Western blotting and amino acid sequencing. By carrying out D1-immunization in rabbits a polyclonal monospecific D1-antiserum was obtained. For the qualitative characterization of D1 as a lipid-binding peptide, the effect of the lipids phosphatidylglycerol (PG), monogalactosyldiacylglyceride (MGDG) and phosphatidylcholine (PC) on PSII-oxygen evolution was analysed in reconstitution experiments. In these experiments purified photosystem II (PSII)-particle preparations were treated with the enzyme phospholipase A2 and supplemented with lipid emulsions. We were able to show that the inhibition of electron transport, as the consequence of this lipase treatment, was only relieved, if phosphatidylglycerol was added to the preparation. A model was proposed, in which phosphatidylglycerol is a functional effector for the optimal conformation of D1 in the PSII core complex. Phosphatidylglycerol molecules are unusually tightly bound to the D1 peptide by hydrophobic interactions. A covalent binding seems not probable. The localisation of phosphatidylglycerol binding sites was found by trypsin treatment of D1 and analysis of the obtained oligopeptides with HPLC and immunoblotting. The binding sites could be confined to the hydrophobic amino acid section between arginine 27 and arginine 225, which is known to be the membrane anchor of D1. This has led us to the conclusion that the phospholipid phosphatidylglycerol plays an important role for anchoring the D1-peptide and for its orientation in the thylakoid membrane. Phosphatidylglycerol with its high amount of palmitic acid has in prokaryotic cyanobacteria apparently a role in stabilization and orientation. The high turn-over of D1 and the spatial separation of the synthesis- and incorporation-site in the membrane, developed during evolution in eukaryotic organisms, might have changed the requirement on the mobility and the orientation of D1 in photosynthetic membranes.
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PMID:The role of phosphatidylglycerol as a functional effector and membrane anchor of the D1-core peptide from photosystem II-particles of the cyanobacterium Oscillatoria chalybea. 754 31


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