Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medicinal leech Hirudo medicinalis produces a low-molecular mass compound with properties similar to those of prostacyclin. It extracted with organic solvent, had affinity to 6-keto-PGF1alpha antibodies, inhibited human platelet aggregation induced in vitro by thrombin (by 50% at 4 pg/ml), and caused hypotension and secretion of plasminogen (t-PA) into the blood stream of rats. A main distinction from prostacyclin is stability of the substance due to covalent binding with the polypeptide chain of destabilase. Because of the high aggregability of destabilase, the molecules of the protein-lipid complex are organized into micelles that can change their spatial orientation depending on the nature of the solvent. Incorporation of hirudin and blood plasma kallikrein inhibitor into the micelle structure causes the formation of liposomes (with a molecular mass of the structural monomer 25 kDa). This complex with polypeptides provides not only stability but also rapid transmembrane penetration. The pure prostacyclin-like substance has a molecular mass of 391 Da and can be produced on destruction of the destabilase polypeptide chain.
 ...
PMID:A stable prostacyclin-like substance produced by the medicinal leech Hirudo medicinalis. 1048 82

The cDNA encoding of a phospholipase A(2) inhibitor (PLIalpha) of the Chinese mamushi, Agkistrodon blomhoffii siniticus, was identified from a liver cDNA library by use of a probe prepared by polymerase chain reaction (PCR) on the basis of the amino acid sequence of PLIalpha. It encoded a polypeptide of 166 amino acid residues, including 19 residues of the signal sequence and 147 residues of the complete mature sequence of PLIalpha. The PLIalpha cDNA was subcloned into the expression vector pET-16b and used to transform Escherichia coli strain BL21(DE3)pLysS. The recombinant PLIalpha expressed as a fusion protein was solubilized and purified to homogeneity by use of a metal affinity resin. The purified PLIalpha fusion protein underwent folding to form a trimeric structure like the intact PLIalpha, and showed inhibitory activity against the group II acidic PLA(2) from A. blomhoffii siniticus venom; although its binding constant (1/K(i)) value was 30-fold lower than that of the natural PLIalpha. The elimination of the N-terminal additional peptide from the fusion protein resulted in a marked increase in the inhibition activity with a binding constant comparable to that of the natural PLIalpha against the acidic PLA(2). Furthermore, the carbohydrate chains of the natural PLIalpha were found to play an important role in the inhibitory activity against the basic PLA(2).
 ...
PMID:cDNA cloning and bacterial expression of phospholipase A(2) inhibitor PLIalpha from the serum of the Chinese mamushi, Agkistrodon blomhoffii siniticus(1). 1052 27

Staphylokinase (SAK), a polypeptide secreted by Staphylococcus aureus, is a plasminogen activator with a therapeutic potential in thrombosis diseases. A Bacillus subtilis strain which is multiply deficient in exoproteases was transformed by an expression plasmid carrying a promoter and a signal sequence of subtilisin fused in frame with the sak open reading frame. However, the amount of SAK secretion was marginal (45 mg/liter). In contrast, disruption of the wprA gene, which encodes a subtilisin-type protease, strongly promoted the production of SAK in the stationary phase (181 mg/liter). In addition, the extracellular stability of mature SAK was dramatically enhanced. These data indicate a significant role of the wprA gene product in degrading foreign proteins, both during secretion and in the extracellular milieu.
 ...
PMID:Enhancement of secretion and extracellular stability of staphylokinase in Bacillus subtilis by wprA gene disruption. 1065 6

Although phospholipase A(2) (PLA(2)) is of importance for insulin secretion, it is not established how it relates to other signalling mechanisms. This study examined the crosstalk between PLA(2) and the cyclic AMP (cAMP)-protein kinase A (PKA) pathway in isolated rat islets. Forskolin, IBMX, and dbcAMP reduced [(3)H]arachidonic acid ([(3)H]AA) efflux from prelabelled islets during PLA(2) activation by mellitin or cholecystokinin (CCK-8), while efflux induced by carbachol was unaffected. The PKA inhibitor myrPKI(14-22) prevented this reduction of CCK-8-induced efflux. Glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and vasoactive intestinal polypeptide (VIP) diminished CCK-8-induced efflux. Also in the absence of Ca(2+), forskolin/IBMX and dbcAMP reduced CCK-8-induced efflux. In parallel with effects on [(3)H]AA, the expected additive insulin secretion induced by mellitin or CCK-8 in combination with forskolin or GLP-1, respectively, was reduced. In conclusion, the cAMP-PKA pathway restrains both Ca(2+)-dependent and Ca(2+)-independent PLA(2) activation, indicating a regulating crosstalk between these two pathways.
 ...
PMID:The cyclic AMP-protein kinase A pathway restrains islet phospholipase A(2) activation. 1069 7

A novel protease with fibrinolytic activity, designated as SW-1, was isolated and purified from the fermentation broth of Streptomyces sp. strain Y405, a soil isolate. The purification procedure involved ammonium sulphate fractionation, decolorization on 290 resin, gel filtration on Sephadex G75, anion-exchange chromatography on DEAE Sephadex A25, and affinity chromatography on Lysine Sepharose 4B. About 4.2 mg purified enzyme was obtained from a liter of fermentation broth and the recovery yield was 12.0%. The purified enzyme showed the specific activity of 2952.3 urokinase units per milligram, which was increased by 230.6 fold over the fermentation broth. The purity determined by HPLC was 83.5%. SW-1 is a single chain polypeptide with a predicted molecular weight of 30 kDa in SDS-PAGE and an isoelectric point of 8.5. The N-terminal sequence of SW-1 is R/N/F-P/D-G-M-T-M-T-A-I-A-N-Q-N-T-Q-I-N. There may be nonhomogeneity in the first and second amino acid residue of its N-terminal sequence. The analysis of amino acid composition showed that SW-1 consisted of 262 amino acids. The fibrinolytic activity of SW-1 was entirely inhibited by 10 mmol/L PMSF, 1 mmol/L EDTA and 1 mol/L lysine, respectively, suggesting that SW-1 is a serine protease and metalloprotease, and that the lysine binding site might play a role in the activity. The fibrinolytic activity of SW-1 is stable between 4-37 degrees C and pH 4.0-9.0, and the optimum pH is 8.0. On plasminogen-free fibrin plates, SW-1 showed the same fibrinolytic activity as the mixture of SW-1 with plasminogen, indicating that SW-1 is a fibrinolytic enzyme which affects fibrin directly, but not a plasminogen activator which affects fibrin by activating plasminogen.
 ...
PMID:Purification and characterization of a novel fibrinolytic enzyme from Streptomyces spp. 1071 27

Homocysteine (HC) is a highly reactive thiol intermediate in amino acid metabolism, which can modify the function of endothelial cells in a myriad of ways. In vitro, homocysteine can inhibit the thromboresistance properties of the endothelial cell by induction of procoagulant factors, inactivation of natural anticoagulant systems, and suppression of vasodilatory and platelet-modulating factors. HC also inhibits the fibrinolytic system by impairing the ability of the endothelial cell to bind tissue plasminogen activator (t-PA), by interacting directly with the t-PA binding "tail" domain of its endothelial cell receptor, annexin II. Moreover, HC influences endothelial cell gene expression as exemplified by induction of the elongation factor-1 family of polypeptides, which promote polypeptide chain elongation during mRNA translation. Induction of EF-1 subunits alpha, beta, gamma and delta by homocysteine is associated with increased turnover of at least one free thiol-containing protein, suggesting that up-regulation of these subunits may represent a mechanism for replacement of damaged or modified proteins. A more complete understanding of the diverse effects of homocysteine on endothelial cell function may provide important clues to the precise role homocysteine may play in the initiation and progression of vascular disease.
 ...
PMID:Inhibition of endothelial cell thromboresistance by homocysteine. 1072 10

Acutohaemolysin, a phospholipase A(2) (PLA(2)) from the venom of the snake Agkistrodon acutus, has been isolated and purified to homogeneity by anion-exchange chromatography on a DEAE-Sepharose column followed by cation-exchange chromatography on a CM-Sepharose column. It is an alkaline protein with an isoelectric point of 10.5 and is comprised of a single polypeptide chain of 13 938 Da. Its N-terminal amino-acid sequence shows very high similarity to Lys49-type PLA(2) proteins from other snake venoms. Although its PLA(2) enzymatic activity is very low, acutohaemolysin has a strong indirect haemolytic activity and anticoagulant activity. Acutohaemolysin crystals with a diffraction limit of 1.60 A were obtained by the hanging-drop vapour-diffusion method. The crystals belong to the space group C2, with unit-cell parameters a = 45.30, b = 59.55, c = 46.13 A, beta = 117.69 degrees. The asymmetric unit contains one molecule.
 ...
PMID:Characterization, crystallization and preliminary X--ray diffraction analysis of acutohaemolysin, a haemolytic toxin from Agkistrodon acutus venom. 1093 Aug 41

A fibrinolytic enzyme, F II(a), was isolated from Agkistrodon acutus venom by ion-exchange chromatography and gel filtration. F II(a) consisted of a single polypeptide chain with a molecular weight of 26,000 and an isoelectric point of 4.6. F II(a) was shown to solubilize fibrin and fibrinogen. F II(a) cleaved, primarily, the alpha chain of fibrinogen and fibrin followed by the beta chain, while the gamma chain was minimally affected. Thus, the enzyme was an alpha,beta-fibrinogenase. The cleavage pattern of fibrinogen clearly varied from plasmin cleavage of the same molecule. In vivo, F II(a) had no influence on the rat's tissue-type plasminogen activator and plasminogen activator inhibitor-1 activities in plasma. At the dosage of 5mg/kg, histological examination of heart, liver and lung tissue showed no hemorrhage. F II(a) is an enzyme that hydrolyzed fibrin directly without hemorrhagic activity.
 ...
PMID:Purification and biochemical characterization of F II(a), a fibrinolytic enzyme from Agkistrodon acutus venom. 1130 23

Aviptadil is an injectable formulation of vasoactive intestinal polypeptide (VIP) in combination with the adrenergic drug phentolamine. Aviptadil in combination with phentolamine and sexual stimulation, is expected to provide a new and effective alternative for erectile dysfunction (ED) patients that is essentially free of the troublesome side effects and cumbersome delivery methods which limit the use of other pharmacologic preparations. Aviptadil can be delivered using Senetek's novel and patented autoinjector (Reliaject), which renders the self-injection process exceptionally easy, unobtrusive to perform and helps ensure accurate, safe delivery of the medication [306380]. In July 1997, Senetek filed a PLA with the Danish Medicines Authority [253591] and its third PLA in Ireland for the treatment of moderate-to-severe, organic-based ED [255084]. In September 1997, Senetek filed PLAs seeking approval to market aviptadil in Switzerland, South Africa and New Zealand 1263505]; by April 2000, it had been approved in New Zealand [361039]. All clinical trials were placed on hold in August 1999 after the FDA advised the MCA of safety concerns regarding a competitor's phentolamine mesylate product (Vasomax; Zonagen Inc/Schering-Plough Corp). At this time, the activities to support the registration of aviptadil in the EU were ongoing and were not impacted by the clinical hold [336510]. In March 2000, after review by an independent clinical pharmacotoxicologist company employed by Senetek, the carcinogenicity observed in animal models was deemed to have no relevance as an indicator of carcinogenic risk in humans. This information was passed to the MCA along with an extensive review of all prior company studies and the medical literature supporting the efficacy and safety of phentolamine mesylate [361039]. In July 2000, the FDA upgraded the status of the aviptadil IND to a partial clinical hold, allowing human studies to be conducted in the US with a limited duration of 3 months and total number of doses not exceeding three per week. The FDA also recommended that Senetek conduct a two-year rodent study of aviptadil as a result of previously reported brown adipose tissue proliferations observed in the course of a competitor's rodent study in which phentolamine mesylate was administered daily [373086]. In August 2000, the MCA lifted the hold on trials stating the findings do not represent a significant carcinogenic risk in man [378615]. In October 2000, marketing approval in the UK was granted by the MCA. Regulatory filings in other European countries are underway to seek pan-European approval for aviptadil under the Mutual Recognition Process [385477].
 ...
PMID:Aviptadil (Senatek). 1156 15

The major lethal toxin in the venom of Bungarus flaviceps has been isolated by ion-exchange chromatography, absorption chromatography and RP-HPLC with a 14-fold purification and an overall yield of 16.5% of the lethal toxicity contained in crude venom. Its sublethal dose (LD(50)) determined in mice weighing 18-20 g was 0.25 (0.19-0.32) microg per mouse. The lethal toxin was pure according to disc- and SDS-PAGE as well as gel HPLC. Its apparent molecular weight determined by SDS-PAGE was 29 kDa. It is a basic protein consisting of two polypeptide chains having apparent molecular weights of 17 and 8 kDa, respectively. The toxin has PLA activity but is free of ACE activity.
 ...
PMID:Isolation of the major lethal toxin in the venom of Bungarus flaviceps. 1173 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>