Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin and its enzymatic fragments, prepared by degradation of heparin with heparinase from Flavobacterium heparinum, were capable of inhibiting the actomyosin-ATPase activity obtained from striated and smooth vascular muscles. Heparin did not inhibit the myosin-ATPase activity in absence of actin. The results show that heparin changes the step of ATP hydrolysis of the complex actomyosin-ATPase by uncoupling the conformational transition on the myosin-head induced by actin upon the nucleotide-binding site. This mechanism is cooperative and dependent on conformational states of actomyosin complex which in turn is regulated by ATP and calcium levels. It was observed that in the presence of ATP, actin does not compete with heparin for binding to myosin showing that heparin and actin have different binding sites on myosin. The binding of heparin and ATP is cooperative suggesting that the nucleotide binding leads to an exposition of a second heparin-binding site. However, in the absence of ATP, actin competes with heparin for a binding site on the myosin. These results strongly suggest that in the weakly binding state of actin to myosin, the binding of heparin is powerful and in the rigor state its binding is decreased.
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PMID:Uncoupling of actomyosin adenosinetriphosphatase by heparin and its fragments. 912 22

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31

Heparin and heparan sulfate fragments, obtained by bacterial heparinase and heparitinases, bearing an unsaturation at C4-C5 of the uronic acid moiety, are able to produce up to 80% reduction of the cytosolic calcium of smooth muscle cell lines. Unsaturated disaccharides from chondroitin sulfate, dermatan sulfate, and hyaluronic acid are inactive, indicating that, besides the unsaturation of the uronic acid, a vicinal 1 --> 4 glycosidic linkage is needed. An inverse correlation between the molecular weight and activity is observed. Thus, the ED(50) of the N-acetylated disaccharide derived from heparan sulfate (430 Da) is 88 microm compared with 250 microm of the trisulfated disaccharide (650 Da) derived from heparin. Except for enoxaparin (which contains an unsaturation at the non-reducing end and 1 --> 4 glycosidic linkage), other low molecular weight heparins and native heparin are practically inactive in reducing the cytosolic calcium levels. Thapsigargin (sarcoplasmic reticulum Ca(2+)-ATPase inhibitor), vanadate (cytoplasmic membrane Ca(2+)-ATPase inhibitor), and nifedipine and verapamil (Ca(2+) channel antagonists) do not interfere with the effect of the trisulfated disaccharide upon the decrease of the intracellular calcium. A significant decrease of the activity of the trisulfated disaccharide is observed by reducing extracellular sodium, suggesting that the fragments might act upon the Na(+)/Ca(2+) exchanger promoting the extrusion of Ca(2+). This was further substantiated by binding experiments and circular dichroism analysis with the exchanger inhibitor peptide.
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PMID:Heparin and heparan sulfate disaccharides bind to the exchanger inhibitor peptide region of Na+/Ca2+ exchanger and reduce the cytosolic calcium of smooth muscle cell lines. Requirement of C4-C5 unsaturation and 1--> 4 glycosidic linkage for activity. 1237 9