Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malnutrition has been associated with changes in cardiac metabolism and performance. We have previously reported a diabetic-type cardiomyopathy associated with chronic food restriction and weight loss. Because the creatine-phosphocreatine-creatine kinase system is important in the contractile process, we studied the components of this system in rats fed a food-restricted diet (33% of control animal intake). After 4 weeks of food restriction, total creatine kinase (CK) activities were reduced by 28% in ventricles and by 38% in atria. The CK isoenzymes in the heart were not equally affected. The BB isoenzyme was decreased by 77% and 78%, the MB isoenzyme by 45% and 43%, the MM isoenzyme by 22% and 19% and CKmito by 16% and 15% in ventricles and atria, respectively. In contrast, brain CK activity which is predominantly the BB isoenzyme, was slightly higher in the food-restricted than in control rats. Further studies on ventricular tissue from food-restricted rats revealed a 27% decline in myofibrillar CR activity and a 58% decline in myofibrillar ATPase activity. Phosphocreatine and creatine concentrations were not changed by food restriction, however, ATP was decreased by 23% in ventricles from rats on the restricted diet. Cardiac mitochondrial oxidative phosphorylation was also impaired. State 3 respiration with alpha-ketoglutarate was reduced 20% in the food-restricted heart. These changes are compared to those which we previously observed in the diabetic rat heart and the significance of these findings is discussed.
J Mol Cell Cardiol 1992 Aug
PMID:Effect of food restriction on the phosphocreatine energy shuttle components in rat heart. 143 12

In Escherichia coli, the ruvA, ruvB and ruvC gene products are required for genetic recombination and the recombinational repair of DNA damage. New studies suggest that these three proteins function late in recombination and process Holliday junctions made by RecA protein-mediated strand exchange. In vitro, RuvA protein binds a Holliday junction with high affinity and, together with RuvB (an ATPase), promotes ATP-dependent branch migration of the junction leading to the formation of heteroduplex DNA. The third protein, RuvC, which acts independently of RuvA and RuvB, resolves recombination intermediates by specific endonucleolytic cleavage of the Holliday junction.
Mol Microbiol 1992 Oct
PMID:Biological roles of the Escherichia coli RuvA, RuvB and RuvC proteins revealed. 143 54

A set of aligned homologous protein sequences is divided into two groups consisting of the most related sequences m and k. The value of the position variability of homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible k x m pairs of amino acid residues in that position divided by k x m. The position variability value plotted vs the sequence position number with a window of 10 positions gives the intergroup local variability profile. The area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area S(r) for 1000 random homologous protein families. If S is greater than S(r) by more than 2 standard deviation units sigma r the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(S(r) + 2 sigma r) are cut off by two straight lines to locate significant regions. The numerical experiment on the family of homologous phospholipases A2 revealed the linear dependence of the values S(r) and sigma r upon the position variability standard deviation sigma v of the homologous sequences. Furthermore, it was shown for protein families of various length (rhodopsins, aspartate aminotransferases, cytochromes b, L- and M-subunits of photosynthetic bacteria photoreaction centre and alpha-subunits of Na, K-ATPase), that delta S = S - n(S'r + 2 sigma r), where S - the area of the local variability profile, n = L/l (L - the length of the given protein family and l - the length of the hypothetical protein domain). If l = 250 then S'r = -1.42 + 62.56 sigma v and sigma'r = -0.14 + 7.46 sigma v.
Mol Biol (Mosk)
PMID:[Localization of conserved and variable segments in amino acid sequences of homologous proteins using a personal computer]. 143 78

The thyroid status markedly influences the contractile function of muscle, and changes in the activity of the Ca2+ ATPase of the sarcoplasmic reticulum (SR) contribute to these alterations. Two separate genes encode the major isoforms of SR Ca2+ ATPase. In fast skeletal muscle, sarcoplasmic endoplasmic reticulum Ca2+ ATPase type 1 (SERCa1) presents the major isoform, whereas in slow skeletal muscle SERCa type 2 (SERCa2) predominates. Cardiac muscle contains only SERCa2. To examine the mechanisms responsible for changes in contractile function, we quantitated SERCa1 and SERCa2 mRNA levels in fast extensor digitorum longus muscle (EDL), slow soleus muscle, and cardiac muscle in rats of different thyroid status. Hypothyroidism led in soleus to a marked decrease in SERCa1 mRNA and SERCa2 mRNA levels, in cardiac muscle SERCa2 mRNA decreased markedly, as previously shown by us, and in EDL SERCa1 mRNA decreased. These findings are compatible with a hypothyroidism induced decrease in SR Ca2+ ATPase activity and a delay in muscle relaxation. In contrast, SERCa2 mRNA of EDL, representing only a small percent of total SERCa mRNA in this muscle, increased to 175% of control values. Muscle specific and SERCa gene specific changes also occur after acute triiodothyronine (T3) administration to hypothyroid rats. T3 does not induce a significant change in SERCa1 or SERCa2 mRNA levels in soleus, but in the heart SERCa2 mRNA increases about 3-fold. In EDL, T3 increases SERCa1 mRNA from a hypothyroid level of 59 +/- 6% to 138 +/- 4% of control values but SERCa2 mRNA is decreased to 75 +/- 5% of control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Sep
PMID:Thyroid hormone response of slow and fast sarcoplasmic reticulum Ca2+ ATPase mRNA in striated muscle. 144 89

The epsilon subunit of the F0F1-ATPase from Escherichia coli has been expressed in E. coli as a fusion protein with glutathione S-transferase from the parasitic helminth Schistosoma japonicum. The epsilon subunit released by thrombin treatment of the purified fusion protein carried two amino acid changes, A1G and M2S, and was obtained in a yield of about five milligrams per litre of cultured cells. The two amino acid changes were shown not to affect function. The protein has been crystallized in a form suitable for X-ray diffraction structure analysis. The crystals are hexagonal, space group P6(1)22 (or P6(5)22), with a = b = 94.9 A, c = 57.1 A and gamma = 120 degrees. The diffraction from small crystals extends to at least 2.9 A resolution.
J Mol Biol 1992 Nov 05
PMID:The expression, purification and crystallization of the epsilon subunit of the F1 portion of the ATPase of Escherichia coli. 144 91

Terminase, the DNA packaging enzyme of phage lambda, binds to lambda DNA at a site called cosB, and introduces staggered nicks at an adjacent site, cosN, to generate the cohesive ends of virion lambda DNA molecules. Terminase also is involved in separation of the cohesive ends and in binding the prohead, the empty protein shell into which lambda DNA is packaged. Terminase is a DNA-dependent ATPase, and both subunits, gpNu1 and gpA, have ATPase activity. cosB contains a series of gpNu1 binding sites, R3, R2 and R1; between R3 and R2 is a binding site, I1, for integration host factor (IHF), the Escherichia coli DNA bending protein. In this work, a series of mutations in Nu1 have been isolated as suppressors of cosB mutations. One of the Nu1 mutations is identical to the previously described Nu1ms1/ohm1 mutation predicted to cause the change L40F in the 181 amino acid-long gpNu1. Three other Nu1 missense mutations, the Nu1ms2 (L40I), ms3 (Q97K) and ms4 (A92G) mutations, have been isolated; the relative strengths of suppression of cosB mutations by the Nu1ms mutations are: ms1 > ms2 > ms3 > ms4. The Nu1 missense mutations all affect amino acid residues that lie outside of the putative helix-turn-helix DNA binding motif of gpNu1. The Nu1ms1 and Nu1ms2 mutations alter an amino acid residue (L40) that lies directly between two segments of gpNu1 proposed to be involved in ATP binding and hydrolysis; thus these mutations are likely to alter the gpNu1 ATP-binding site. The Nu1ms3 and Nu1ms4 mutations both affect amino acid residues in the central region of gpNu1 that is predicted to form a hydrophilic alpha-helix. To explain how the Nu1ms mutations suppress cosB defects, models involving alterations of the DNA binding and/or catalytic properties of terminase are considered. The results also indicate that terminase occupancy of a single gpNu1 binding site (R3) is necessary and sufficient for the efficient initiation of DNA packaging; the Nu1ms1, ms2 and ms3 mutations permit IHF-independent plaque formation by a phage lacking R2 and R1.
J Mol Biol 1992 Nov 05
PMID:Genetic analysis of mutations affecting terminase, the bacteriophage lambda DNA packaging enzyme, that suppress mutations in cosB, the terminase binding site. 144 96

Previous studies have identified changes of mechanical properties of airway smooth muscle (ASM) from a canine model of atopic airway hyperreactivity. These changes, including increased maximum shortening capacity (delta Lmax) and early shortening velocity (Vo), may be responsible for the airway hyperresponsiveness in asthma. We have suggested that these changes may be due to increased actomyosin ATPase activity, controlled via phosphorylation of the 20 kD myosin light chain (MLC20) by MLC kinase (MLCK). Therefore, ATPase activity, MLC20 phosphorylation, and MLCK content and activity were assessed in tracheal and bronchial smooth muscles (TSM and BSM) of ragweed pollen-sensitized dogs (S) and their littermate controls (C). Specific ATPase activities from STSM and SBSM were significantly higher than their control counterparts (CTSM, CBSM). Phosphorylation of MLC20 in STSM was greater both at rest and during electrical stimulation due to the increased amount of MLCK in STSM and SBSM by 30 and 25%, respectively. MLCK activity was also increased significantly in STSM and SBSM (from 46.99 +/- 8.33 and 42.85 +/- 5.92 to 91.9 +/- 6.43 and 64.12 +/- 7.88 32P mmol/mg fresh tissue weight/min respectively [mean +/- SEM]). When normalized to the amount of MLCK in the tissue, however, specific MLCK activity in STSM and SBSM was similar to that in controls. It is unlikely that myosin phosphatase plays any role in the changes of MLC20 phosphorylation in sensitized animals. Peptide mapping showed no visible change in primary structure of MLCK in STSM and SBSM compared with those of controls. We report that ASM actomyosin ATPase activity is increased in STSM and SBSM. The increased ATPase activity is the result of increased MLC20 phosphorylation, the latter likely resulting from the increased MLCK content, which may account for the hyperresponsiveness found in ASM from these animals.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Ragweed sensitization-induced increase of myosin light chain kinase content in canine airway smooth muscle. 144 4

The Ca(2+)-ATPase of skeletal sarcoplasmic reticulum was purified and reconstituted in proteoliposomes containing phosphatidylcholine (PC). When reconstitution occurred in the presence of PC and the acidic phospholipids, phosphatidylserine (PS) or phosphatidylinositol phosphate (PIP), the Ca(2+)-uptake and Ca(2+)-ATPase activities were significantly increased (2-3 fold). The highest activation was obtained at a 50:50 molar ratio of PS:PC and at a 10:90 molar ratio of PIP:PC. The skeletal SR Ca(2+)-ATPase, reconstituted into either PC or PC:PS proteoliposomes, was also found to be regulated by exogenous phospholamban (PLB), which is a regulatory protein specific for cardiac, slow-twitch skeletal, and smooth muscles. Inclusion of PLB into the proteoliposomes was associated with significant inhibition of the initial rates of Ca(2+)-uptake, while phosphorylation of PLB by the catalytic subunit of cAMP-dependent protein kinase reversed the inhibitory effects. The effects of PLB on the reconstituted Ca(2+)-ATPase were similar in either PC or PC:PS proteoliposomes, indicating that inclusion of negatively charged phospholipid may not affect the interaction of PLB with the skeletal SR Ca(2+)-ATPase. Regulation of the Ca(2+)-ATPase appeared to involve binding with the hydrophilic portion of phospholamban, as evidenced by crosslinking experiments, using a synthetic peptide which corresponded to amino acids 1-25 of phospholamban. These findings suggest that the fast-twitch isoform of the SR Ca(2+)-ATPase may be also regulated by phospholamban although this regulator is not expressed in fast-twitch skeletal muscles.
Mol Cell Biochem 1992 Sep 08
PMID:Regulation of the skeletal sarcoplasmic reticulum Ca(2+)-ATPase by phospholamban and negatively charged phospholipids in reconstituted phospholipid vesicles. 146 Dec 59

The structure of the Neurospora crassa plasma membrane H(+)-ATPase has been investigated using a variety of chemical and physiochemical techniques. The transmembrane topography of the H(+)-ATPase has been elucidated by a direct, protein chemical approach. Reconstituted proteoliposomes containing purified H(+)-ATPase molecules oriented predominantly with their cytoplasmic surface facing outward were treated with trypsin, and the numerous peptides released were purified by HPLC and subjected to amino acid sequence analysis. In this way, seventeen released peptides were unequivocally identified as located on the cytoplasmic side of the membrane, and numerous intervening segments could be inferred to be cytoplasmically located by virtue of the fact that they are too short to cross the membrane and return between sequences established to be cytoplasmically located. Additionally, three large membrane-embedded segments of the H(+)-ATPase were isolated using our recently developed methods for purifying hydrophobic peptides, and identified by amino acid sequence analysis. This information established the topographical location of virtually all of the 919 residues in the H(+)-ATPase molecule, allowing the formulation of a reasonably detailed model for the transmembrane topography of the H(+)-ATPase polypeptide chain. Separate studies of the cysteine chemistry of the H(+)-ATPase have demonstrated the existence of a single disulfide bridge in the molecule, linking the NH2- and COOH-terminal membrane-embedded domains. And, analyses of the circular dichroism and infrared spectra of the purified H(+)-ATPase have elucidated the secondary structure composition of the molecule. A first-generation model for the tertiary structure of the H(+)-ATPase based on this information and other considerations is presented.
Mol Cell Biochem 1992 Sep 08
PMID:Probing the structure of the Neurospora crassa plasma membrane H(+)-ATPase. 146 Dec 58

The potassium-translocating Kdp-ATPase of Escherichia coli shares common functional properties with eukaryotic P-type ATPases. The KdpB subunit has been identified as the catalytic subunit forming the phosphorylated intermediate. Substitution of Asp-307 in KdpB by Glu, Asn, Gln, Tyr, His, Ala or Ser by site-directed mutagenesis and the subsequent transfer of the point mutations to the chromosome revealed that the mutants were not functioning with respect to cell growth at low K+ concentrations and ATPase activity as well as phosphorylation capacity of the purified Kdp complex. These findings indicate that Asp-307 in KdpB is the phosphorylation site of the Kdp-ATPase. In contrast, replacement of the close but non-conserved Asp-300 by Asn or Glu has no immediate influence on the enzyme functions tested. However, the Km for K+ of the ATPase activity has been increased 30-fold compared with the wild-type enzyme.
Mol Microbiol 1992 Dec
PMID:The phosphorylation site of the Kdp-ATPase of Escherichia coli: site-directed mutagenesis of the aspartic acid residues 300 and 307 of the KdpB subunit. 147 95


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