Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Troponin has been prepared from the asynchronous flight muscle of Lethocerus (water bug) taking special care to prevent proteolysis. The regulatory complex contained tropomyosin and troponin components. The troponin components were Tn-C (18,000 Mr), Tn-T (apparent Mr 53,000) and a heavy component, Tn-H (apparent Mr 80,000). The troponin was tightly bound to tropomyosin and could not be dissociated from it in non-denaturing conditions. A complex of Tn-T, Tn-H and tropomyosin inhibited actomyosin ATPase activity and the inhibition was relieved by Tn-C from vertebrate striated muscle in the presence of Ca2+. However, unlike vertebrate Tn-I, Tn-H by itself was not inhibitory. Monoclonal antibodies were obtained to Tn-T and Tn-H. Antibody to Tn-T was used to screen an expression library of Drosophila cDNA cloned in lambda phage. The sequence of cDNA coding for the protein was determined and hence the amino acid sequence. The Drosophila protein has a sequence similar to that of vertebrate skeletal and cardiac Tn-T. The sequence extends beyond the carboxyl end of the vertebrate sequences, and the last 40 residues are acidic. Part of the sequence of Drosophila Tn-T is homologous to the carboxyl end of the Drosophila myosin light chain MLC-2 and one anti-Tn-T antibody cross-reacted with the light chain. Lethocerus Tn-H is related to the large tropomyosins of Drosophila flight muscle, for which the amino acid sequence is known, since antibodies that recognize this component also recognize the large tropomyosins. Tn-H is easily digested by calpain, suggesting that part of the molecule has an extended configuration. Electron micrographs of negatively stained specimens showed that Lethocerus thin filaments have projections at about 39 nm intervals, which are not seen on thin filaments from vertebrate striated muscle and are probably due to the relatively large troponin complex. Decoration of the thin filaments with myosin subfragment-1 in rigor conditions appeared not to be affected by the troponin. The troponin of asynchronous flight muscle lacks the Tn-I component of vertebrate striated muscle. Tn-H occurs only in the flight muscle and may be involved in the activation of this muscle by stretch.
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PMID:Troponin of asynchronous flight muscle. 285 58

The relaxant effects of amiloride and its analogues, benzamil, 5-(N,N-diethyl)-amiloride (DEAM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIAM), were investigated using smooth muscle of guinea-pig taenia caeci and chicken gizzard. High K+-induced contractions of intact taenia and gizzard were inhibited by these compounds (1-100 microM) with the order of potency; benzamil greater than or equal to EIAM greater than DEAM greater than amiloride. Contractions of permealized taenia and gizzard were also inhibited by these compounds at concentrations 8-35 times higher than those needed to inhibit the contractions of intact tissues. These compounds inhibited 20 K myosin light chain (MLC) phosphorylation at the concentrations needed to inhibit the contraction in the permealized muscles. Calmodulin (CaM) activity, as monitored by erythrocyte membrane (Ca2+ + Mg2+)-ATPase and phosphodiesterase activities, was inhibited by DEAM and EIAM at similar concentrations as those to inhibit the MLC phosphorylation. Benzamil also inhibited CaM activity at concentrations 4-8 times higher than those required to inhibit MLC phosphorylation. However, amiloride failed to inhibit CaM activity. Among these compounds, amiloride and benzamil inhibited Ca2+/CaM-independent MLC phosphorylation due to trypsin-treated MLC kinase. Taenia tissue gradually accumulated these compounds and the tissue/medium ratio exceeded 3.5-17 after a 3-hr incubation period. These results indicate that amiloride and its analogues inhibit smooth muscle contraction mainly by the direct inhibition of MLC phosphorylation. The inhibitory effect of amiloride may be attributable to the inhibition of MLC kinase, whereas the inhibitory effect of DEAM and EIAM may largely be attributable to the inhibition of CaM. Benzamil may inhibit contraction by the inhibition of both MLC kinase and CaM. Differences in the drug-sensitivity between intact and permealized tissues may be attributable to the difference in drug accumulation by the cell.
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PMID:Direct inhibition of contractile apparatus by analogues of amiloride in the smooth muscle of guinea-pig taenia caecum and chicken gizzard. 293 May 91

Caldesmon induces inhibition of MG2+-ATPase activity of actomyosin and relaxation of skinned fibers of chicken gizzard smooth muscle without influencing the level of myosin light chain-1 phosphorylation. Both these effects are reversed by calmodulin at a high molar excess over caldesmon in the presence of Ca2+.
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PMID:Caldesmon-induced inhibition of ATPase activity of actomyosin and contraction of skinned fibres of chicken gizzard smooth muscle. 293 46

Because of the potential of dihydropyridine calcium channel blockers in the management of premature labor, we have studied the direct effects of nitrendipine on actomyosin in the pregnant and nonpregnant uterus and in the term human placenta. Actomyosin adenosinetriphosphatase in the three tissues and another model of actin-myosin interaction, superprecipitation of placental actomyosin, were inhibited by nitrendipine. The inhibition was not diminished by high concentrations of calcium. To identify the mechanism, placental myosin was phosphorylated in the absence and presence of 0.8 X 10(-4) mol/L of nitrendipine. The myosin phosphorylated in the presence of nitrendipine had lower actin-activated adenosinetriphosphatase, which is consistent with the inhibition of myosin light chain phosphorylation. However, nitrendipine did not affect the adenosinetriphosphatase activity of myosin nor did further reduce the adenosinetriphosphatase of the already phosphorylated placental actomyosin. Thus nitrendipine inhibition is directed to the phosphorylation reaction but not to the adenosinetriphosphatase site of myosin. Myometrial relaxation in vivo or in vitro occurs at the pharmacologic nitrendipine levels of 10(-9) to 10(-8) mol/L, which is at least 10,000 times lower than that of the concentration of 50% inhibition of myosin light chain phosphorylation (0.0026 +/- 0.00015 mol/L of nitrendipine, mean +/- SEM) demonstrated in the present work. Because of this difference, the direct intracellular actions of dihydropyridine calcium channel blockers are not expected to cause adverse effects in the uteroplacental system when these drugs are used in the prevention or treatment of premature labor.
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PMID:Pharmacologic levels of nitrendipine do not affect actin-myosin interaction in the human uterus and placenta. 293 50

The effect of phosphorylation in skeletal myosin light chain (LC2) on the actomyosin and acto-heavymeromyosin (HMM) ATPase activities was investigated in the presence or absence of regulatory proteins (tropomyosin-troponin complex). Phosphorylation in LC2 did not modulate the actin-myosin and actin-HMM interactions over a wide range of KCl concentrations from 30 to 150 mM without regulatory proteins. In the presence of regulatory proteins, phosphorylation in myosin LC2 enhanced the ATPase activity of actomyosin with calcium ions, but the removal of calcium ions made little difference in the ATPase activity between phosphorylated and dephosphorylated myosins. Ca2+-sensitivity of the regulated actomyosin was slightly changed by phosphorylation in myosin LC2. However, both the ATPase activity and Ca2+-sensitivity of the regulated acto-HMM were unaffected by phosphorylation in HMM LC2.
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PMID:Phosphorylation in skeletal myosin light chain modulates the actin--myosin interaction in the presence of regulatory proteins in vitro. 293 71

The crude actomyosin precipitate from sea urchin (Arbacia punctulata) egg extracts contains Ca2+-sensitive myosin light chain kinase activity. Activity can be further increased by exogenous calmodulin (CaM). Egg myosin light chain kinase activity is purified from total egg extract by fractionating on three different chromatographic columns: DEAE ion exchange, gel filtration on Sephacryl-300, and Affi-Gel-CaM affinity. The purified egg kinase depends totally on Ca2+ and CaM for activity. Unphosphorylated egg myosin has very little actin-activated ATPase. After phosphorylation of the phosphorylable light chain by either egg kinase or gizzard myosin light chain kinase, the actin-activated ATPase of egg myosin is enhanced several fold. However, the egg kinase bears some unique characteristics which are very different from conventional myosin light chain kinases of differentiated tissues. The purified egg kinase has a native molecular mass of 405 kDa, while on sodium dodecyl sulfate-polyacrylamide electrophoresis it shows a single subunit of 56 kDa. The affinity of egg kinase for CaM (Ka = 0.4 microM) is relatively weaker than that of the gizzard myosin light chain kinase. The egg kinase autophosphorylates in the presence of Ca2+ and CaM and has a rather broad substrate specificity. The possible relationship between this egg Ca2+-CaM-dependent kinase and the Ca2+-CaM-dependent kinases from brain and liver is discussed.
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PMID:Purification and characterization of a sea urchin egg Ca2+-calmodulin-dependent kinase with myosin light chain phosphorylating activity. 293 87

Experimental myotonia was induced by feeding rats with 20,25-diazacholesterol for up to 8 months. Histochemical analysis of myotonic extensor digitorum longus (EDL) muscle showed a progressive decrease of type IIB fibres and a concomitant increase of type IIA and type I fibres. A transient hypertrophy of type IIA fibres was observed 6 months after beginning the treatment. Analysis of the pattern of myosin light chains of single fibres from EDL showed that myotonia caused a progressive decrease of fibres showing a pure fast myosin light chain pattern and an increase of fibres showing coexistence of fast and slow myosin light chains (intermediate fibres). Only a small percentage of intermediate fibres showed coexistence of fast and slow myosin heavy chains. Myotonic fibres presented an increased sensitivity to caffeine which approached that of normal soleus fibres. Furthermore, sarcoplasmic reticulum (SR) vesicles isolated from hind limb fast muscles of myotonic rats demonstrated a decrease of Ca2+-dependent ATPase and Ca2+-transport activities as well as a decrease of immunoreactivity with anti-rabbit SR fast Ca2+-ATPase antibody. These results suggest that the increased electrical activity brought about by 20,25-diazacholesterol-induced myotonia, caused a fast to slow transition in the phenotypic expression of myosin and sarcoplasmic reticulum proteins.
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PMID:Fast to slow transition induced by experimental myotonia in rat EDL muscle. 293 75

The purpose of this study was to examine the distribution of myosin isozymes in rodent (Rattus norvegicus) hindlimb skeletal muscles and regions of muscle known to have contrasting fiber-type composition. Muscle samples were analyzed for Ca2+-regulated myofibril adenosine triphosphatase (ATPase) activity, Ca2+-activated myosin ATPase activity, myosin isozyme profile, and myosin light chain profile. Four isozymes of myosin were identified based on native protein and light chain electrophoresis patterns: one associated primarily with slow-twitch muscle (SM) and three associated primarily with fast-twitch muscle (FM). Multiple linear regression analysis of Ca2+-regulated myofibril ATPase activity (pCA 4) vs. measured isozyme profile was used to estimate the myofibril ATPase activities of the individual isozymes (FM1 = 0.86, FM2 = 0.52, FM3 = 0.31, and SM = 0.15 mumol Pi formed . mg myofibril protein-1 . min-1 at 25 degrees C, n = 180, P less than 0.001). Differences in the native isozyme profiles and myofibril ATPase activities between muscles and muscle regions of similar fiber type composition indicate that a given fiber type may not necessarily express a single isozyme profile. These data are consistent with the hypothesis that, among rodent hindlimb skeletal muscles and inherently their motor units, a range of myosin isozyme profiles exists that may provide a broad range of mechanical expression.
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PMID:Myosin isozyme distribution in rodent hindlimb skeletal muscle. 294 6

The abilities of several calmodulin antagonists and other compounds belonging to different pharmacological classes to modulate Ca2+ X calmodulin mediated arterial myosin light chain phosphorylation and Ca2+-troponin C regulated cardiac myofibrillar ATPase activity have been quantitated in Triton X-100 purified preparations of bovine aortic actomyosin and canine ventricular myofibrils. At submaximal free Ca2+ concentrations, all calmodulin antagonists inhibited myosin phosphorylation; however, some (calmidazolium, trifluoperazine, chlorpromazine, pimozide) stimulated myofibrillar ATPase activity, some (compound 48/80, W-5) had no effect on activity, while others (W-7, haloperidol, mastoparan) inhibited ATPase activity. The relative order of potency for several agents in both preparations was the same, as IC50 values for inhibition of arterial myosin phosphorylation were: calmidazolium, 0.5 microM; trifluoperazine, 22 microM; perhexiline, 35 microM; and concentrations which stimulated cardiac myofibrillar ATPase activity by 50% were: calmidazolium, 9 microM; trifluoperazine, 45 microM; perhexiline, 90 microM. A common feature of stimulation of cardiac ATPase activity by these agents was a leftward shift in the pCa relationship, although different shape changes in the pCa curves were also apparent. Maximum ATPase activity was either not affected or inhibited (trifluoperazine). Several other agents belonging to diverse pharmacological classes also had differential effects on myosin phosphorylation and ATPase activity. These results show that structurally-distinct calmodulin antagonists and other compounds differentially affect cardiac myofibrillar ATPase activity. Moreover, several agents have been identified which inhibit arterial, and stimulate cardiac, contractile protein regulatory mechanisms. Thus, it may be possible to develop mechanistically novel cardiotonic/vasodilator agents, Ca2+ binding protein modulators, which function primarily by altering the Ca2+ sensitivity of contractile protein interactions.
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PMID:Modulation of vascular and cardiac contractile protein regulatory mechanisms by calmodulin inhibitors and related compounds. 294 84

Actomyosin in smooth muscle is in a quiescent state. The mechanism or mechanisms by which Ca2+ activates the actomyosin ATPase is not clear. There is sufficient evidence for the presence of enzyme systems which phosphorylate and dephosphorylate myosin light chains. The activity of the kinase that phosphorylates the myosin is regulated by cAMP-dependent protein kinase. Phosphorylated kinase has decreased affinity for calmodulin and lower activity when compared with unphosphorylated myosin light chain kinase. The activity of myosin light chain kinase is also regulated by calcium-calmodulin. In the presence of Ca2+, myosin is phosphorylated. In the absence of Ca2+, the phosphatase activity becomes dominant; the myosin remains in the unphosphorylated form under this condition. The Mg2+-ATPase of the phosphorylated myosin is activated by actin. The maximal activation of the Mg2+-ATPase by actin requires Ca2+ and tropomyosin, a protein located on the thin filament. Hence, the actin-activation of the Mg2+-ATPase requires Ca2+ even after phosphorylation by the calcium-calmodulin dependent kinase. The regulation of actin-activated ATPase activity by myosin light chain phosphorylation is depicted in the schematic diagram. Caldesmon, an actin-binding protein which also binds to calmodulin in the presence of Ca2+, has been shown to be present in thin-filaments isolated from smooth muscle. This protein inhibits actin-activated myosin ATPase activity. The release from this inhibition requires Ca2+ and calmodulin. The possibility that caldesmon is also involved in the calcium regulation of actomyosin in smooth muscle is presently under investigation in a number of laboratories.
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PMID:Regulation of actomyosin ATPase in smooth muscle. 294 44


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