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)

A comparison of Cu K-edge x.a.f.s. spectra with that of the equivalent Fe K-edge for chicken ovotransferrin (COT) indicates that the metal ions occupy essentially the same binding sites in the protein. However, in the case of the Cu2+ complex the metal appears to have reduced co-ordination. Changes are observed in the x.a.f.s. of 90%-saturated COT (Cu1.8COT) on freeze-drying. The three-dimensional X-ray structures of rabbit serum transferrin and human lactoferrin have shown that the ferric cations are co-ordinated by four protein ligands and a bidentate carbonate anion in a distorted octahedral arrangement [Anderson, Baker, Dodson, Norris, Rumball, Waters & Baker (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1768-1774; Anderson, Baker, Norris, Rice and Baker (1989) J. Mol. Biol. 209, 711-734; Bailey, Evans, Garratt, Gorinsky, Hasnain, Horsburgh, Jhoti, Lindley, Mydin, Sarra & Watson (1988) Biochemistry 27, 5804-5812]. This structural information, together with the differences in e.x.a.f.s. spectra for solution and freeze-dried samples of diferric COT [Hasnain, Evans, Garratt & Lindley (1987) Biochem. J. 247, 369-375] suggests that the synergistic carbonate anion may be capable of behaving as a unidentate linkage to the Cu2+ in the dicupric complex. Data for Cu1.8COT are consistent with only three protein ligands bound to Cu2+, monodentate binding of the synergistic anion in one lobe and its bidentate binding in the other lobe. Such flexibility in the anion co-ordination may be a requirement for the uptake and release of metals by the transferrins.
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PMID:X.a.f.s. studies of chicken dicupric ovotransferrin. 166 Feb 64

Type II alveolar epithelial cells in suspension have been previously shown to possess a Na(+)-H+ antiporter that modulates recovery from an intracellular acid load in the nominal absence of HCO-3 [E. Nord, S. Brown, and E. Crandall. Am. J. Physiol. 252 (Cell Physiol. 21): C490-C498, 1987]. Such a Na(+)-dependent mechanism has also been demonstrated in cultured type II cell monolayers (K. Sano et al. Biochim. Biophys. Acta 939: 449-458, 1988). It has recently been suggested that cultured type II cells possess a H(+)-ATPase that contributes to recovery from an intracellular acid load [R. Lubman, S. Danto, and E. Crandall. Am. J. Physiol. 257 (Lung Cell. Mol. Physiol. 1): L438-L445, 1989]. The present study was undertaken to investigate and characterize the mechanisms by which cultured type II cells recover from an intracellular acid load in the nominal absence of HCO-3. Cultured type II cell monolayers were loaded with the pH-sensitive probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein, and the characteristics of recovery from an imposed intracellular acid load were studied. Recovery of intracellular pH (pHi) was found to be strictly Na(+)-dependent and inhibited greater than or equal to 95% by 1 mM amiloride. Initial rate of recovery was highly sensitive to pHi, with recovery rates varying inversely with increasing pHi. An acidic extracellular pH (6.5) abolished pHi recovery. Treatment of type II cells with either the sulfhydryl reagent N-ethylmaleimide, a nonspecific sulfhydryl reagent, or 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, a specific vacuolar H(+)-ATPase inhibitor at the concentration tested, resulted in marginal but not statistically significant decrements in pHi recovery. Intracellular ATP depletion, using KCN or replacement of glucose by a nonmetabolizable glucose analogue, reduced pHi recovery by 70-75% relative to control values. Sensitivity to ATP was apparent even under conditions that preserved the transmembrane Na+ gradient. Taken together, these data are most consistent with a single mechanism for pHi recovery in the absence of HCO3-. We interpret this mechanism to be an ATP-sensitive Na(+)-H+ antiporter that acts to reestablish pHi in type II alveolar epithelial cells.
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PMID:ATP-sensitive Na(+)-H+ antiport in type II alveolar epithelial cells. 166 8

Effects of the s.c. administration of various doses of estradiol propionate (E.P.; 25-500 micrograms/kg) on the activities of carbonic anhydrase (CA), Mg(2+)-dependent ATPase and Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) in rat duodenal mucosa and kidney cortex, and on body weight, organ weight and serum concentrations of testosterone and estradiol-17 beta, were examined in adult male, female, testectomized and ovariectomized rats. In normal male rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the kidney were increased in a dose-dependent manner and reached 1.6- and 2-fold of controls, respectively, after consecutive administration (daily for 7 days) of 500 micrograms E.P. with no changes in either enzyme activities in duodenal mucosa. The positive correlations (P less than 0.01) were observed by linear regression analysis between serum concentration of estradiol-17 beta and kidney cytosol CA or kidney brush border Mg(2+)-HCO3(-)-ATPase activities. In normal female rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the duodenal mucosa, and brush border Mg(2+)-HCO3(-)-ATPase activity in the kidney were increased by E.P. administration (100 and 500 micrograms/kg, daily for 7 days), however, kidney cytosol CA activity did not change by any dosage. Behavior of a part of both enzymes to E.P. in testectomized rats was altered almost in the same way to that observed in normal female rats and vice versa in ovariectomized rats. Body weight was decreased, in general, by consecutive administration of E.P. in a dose-dependent manner, and kidney weight was increased by E.P. in both male and female rats.
J Steroid Biochem Mol Biol 1991 Sep
PMID:Sexual difference and organ specificity of the effect of estradiol on carbonic anhydrase and Mg(2+)-HCO3(-)-ATPase activities isolated from duodenal mucosa and kidney cortex of male and female rats: preliminary study with crude enzyme samples. 183 40

The purified Ca2+/Mg2+ ATPase from rat heart plasma membrane was activated by Ca2+ and Mg2+ with Ka values of 1.47 mM and 2.51 mM, respectively; other divalent cations also activated the enzyme but to a lesser extent. Divalent cations like Cu2+, Zn2+, Ni2+, Cd2+ were potent inhibitors of the enzyme activity in the presence of Ca2+ or Mg2+ whereas Na+, K+ or HCO3- did not affect the Ca2+/Mg2+ ATPase activity; the pH optima was 8.5. The enzyme hydrolyzed ATP with a Km of 0.34 mM for Ca2+ ATPase and 0.48 mM for Mg2+ ATPase; various nucleoside triphosphate such as ITP, CTP, GTP, and UTP were also hydrolyzed. Phospholipase A and C as well as neuraminidase decreased the Ca2+/Mg2+ ATPase activity whereas phospholipase D was ineffective. The purified Ca2+/Mg2+ ATPase was found to bind ATP-r-35S with two affinities; the KD values were 50.9 +/- 0.8 and 1160 +/- 198 nM and the Bmax values were 8.71 +/- 0.16 and 145 +/- 9.7 nmol/mg protein for high and low affinity sites, respectively. Treatment of the enzyme preparation with phospholipases and neuraminidase did not affect the ATP-r-35S binding. Ca2+ was also found to bind with Ca2+/Mg2+ ATPase with a KD of 0.384 mM and a Bmax of 1.85 mumol/mg protein; Ni2+, Mn2+, Zn2+ at 1 mM concentrations inhibited the Ca2+ binding but Mg2+ and verapamil were without effect. Phospholipase A and neuraminidase decreased the Ca2+ binding by 20-30%; this indicated that Ca2+ binding with the purified enzyme may be partly due to the phospholipids and sialic acid residues associated with the enzyme. These results show that the purified Ca2+/Mg2+ ATPase is a Ca2+ binding glycoprotein having two binding sites for ATP. Furthermore, this study suggests that phospholipids associated with purified Ca2+/Mg2+ ATPase are required for maximal activity.
Mol Cell Biochem 1991 Oct 16
PMID:Characterization of the purified rat heart plasma membrane Ca2+/Mg2+ ATPase. 183 90

Experiment I was designed to determine if cell-free synchronous uterine flushings contain an embryotoxic substance that is normally screened by the intact zona pellucida. Sixty 4-cell embryos were allocated to three treatment groups: 1) control embryos (n = 20) were cultured in Modified Kreb's Ringer Bicarbonate medium + 10% bovine calf serum (mKRB-BCS), 2) UF embryos (n = 20) were cultured in 80% mKRB-BCS + 20% sterile dialyzed uterine flushings (UF), 3) MicroUF embryos (n = 20) received a microsurgical incision in the zona pellucida and were cultured in 80% mKRB-BCS + 20% UF. Following 72 h in culture at 37 degrees C under a 90% N2, 5% CO2, and 5% O2 atmosphere, the number of nuclei/embryo and the incidence of protrusion of the trophoblast through the zona pellucida (PTZ) were recorded. Addition of UF had no effect on embryo development. A greater (P less than .005) proportion of MicroUF embryos exhibited PTZ as compared to UF and control embryos. Experiment II was devised to further characterize the occurrence of PTZ in Micro porcine embryos. Thirty-three 4- to 10-cell embryos and 14 morulae were distributed across two treatments: 1) control embryos (n = 16 and 6, respectively) were cultured as described in Experiment I; and 2) micro embryos were treated similarly to MicroUF embryos in Experiment I but were cultured in mKRB-BCS only. At the onset of PTZ, embryos were immediately fixed and examined. The proportion of embryos exhibiting PTZ was greater (P less than .007) for Micro versus control embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1991 Oct
PMID:Effect of cell-free synchronous uterine flushings and microsurgery on the development of porcine embryos in vitro. 195 24

As part of a comparative study on the binding of different metals and anions by human lactoferrin, we have prepared and crystallized: (1) dicupric lactoferrin with Cu2+ and carbonate in each site (Cu2Lf); and (2) a lactoferrin complex with Cu2+ and carbonate in one site, and Cu2+ and oxalate in the other (Cu2oxLf). Crystals of Cu2Lf are orthorhombic: a = 155.9, b = 97.0, c = 56.0 A, space-group P2(1)2(1)2(1); those of Cu2oxLf are also orthorhombici a = 155.9, b = 97.1, c = 56.2 A, space-group P2(1)2(1)2(1). Both are isomorphous with diferric human lactoferrin, Fe2Lf. Diffractometer data to 2.6 A and 2.5 A have been collected for Cu2Lf and Cu2oxLf, respectively. Difference maps show that the main effect of substitution of Cu2+ for Fe3+ is a small shift (0.5 to 1.0 A) in the metal position in each site. For Cu2oxLf the oxalate ion is found to be accommodated in the C-lobe, bound to copper in a bidentate mode, causing only small local changes, in the positions of adjacent Arg and Tyr side-chains.
J Mol Biol 1991 May 20
PMID:Preliminary crystallographic studies of copper(II)- and oxalate-substituted human lactoferrin. 203 52

The addition of glucose to suspensions of HIT-T15 insulinoma cells caused a small, transient acidification followed by a gradual, progressive alkalinisation, as assessed by the fluorescent pH-sensitive dye 2',7'-biscarboxyethyl-5'-(6')-carboxyfluorescein (BCECF). Treatment of cells with acetate or lactate produced an immediate, marked acidification followed by recovery and a subsequent alkalinisation. In contrast, addition of NH4Cl caused a rapid rise in intracellular pH (pHi) and recovery to resting values. In cells where Na+/H+ exchange was inhibited, either with amiloride or by omission of Na+ from the medium, glucose caused a progressive acidification, whilst recovery from acetate- or lactate-induced acidification was prevented. Under sodium-free conditions, recovery from acidification could be initiated by addition of Na+. Inhibition of HCO3-/Cl- exchange by pretreatment with 4,4'-diisothiocyanatostilbene 2,2'-disulphonic acid (DIDS), or by omission of HCO3- or Cl- from the medium did not affect any of the changes in pHi elicited by the above agents. It is concluded that the principal mechanism responsible for pHi regulation in HIT-T15 cells is the Na+/H+ antiporter and that the HCO3-/Cl- exchange systems make little, if any, contribution.
Mol Cell Endocrinol 1990 May 28
PMID:Na+/H+ exchange is responsible for intracellular pH regulation in insulin-secreting HIT-T15 cells. 216 30

A plasmid, pWEH1, was constructed containing a fusion of the DNA encoding the signal sequence of the Escherichia coli outer-membrane protein A to the 5'-end of a glyceraldehyde-3-phosphate dehydrogenase cDNA from Ricinus communis. When expressed in E. coli, the fusion protein was secreted by the normal membrane-potential-dependent pathway. Processing by signal peptidase was inhibited by low concentrations of phenethyl alcohol. Quantitative cell fractionation was used to show that the mature plant protein was associated with the bacterial outer membrane. The protein could not be released from the membrane by washing with alkaline sodium carbonate. Radioactivity from [U-14C]-palmitate was incorporated into the heterologous protein. These results suggest that the sequence of this normally cytoplasmic enzyme contains a cryptic lipid-modification site, and the combination of a signal sequence plus a lipid-modification sequence results in specific targeting to the bacterial outer membrane.
Mol Microbiol 1990 Aug
PMID:Secretion of Ricinus communis glyceraldehyde-3-phosphate dehydrogenase by Escherichia coli. 228 Jun 87

Swelling of brain slices is shown to occur in response to elevated potassium levels or glutamate, which is accompanied by astrocytic swelling. Cl-/HCO3- anion exchange inhibitors, such as SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) or furosemide, but not the specific cotransport inhibitor bumetanide, inhibit swelling or increased ion uptake in rat brain slices caused by elevated potassium although there were marked species differences in sensitivity. A novel anion exchange inhibitor, L-644,711, inhibits swelling and increased ion uptake caused by glutamate in rat and cat brain slices, as well as inhibiting [3H]glutamate uptake in primary rat astrocyte cultures. Possible mechanisms of action of the inhibitors are discussed. L-644,711 was also found to be effective in promoting recovery from a trauma plus hypoxia head injury model in cats. Marked perivascular astrocytic swelling is associated with this head injury model, and L-644,711 also inhibited such astroglial swelling as determined ultrastructurally. The significance of these findings in relation to possible connections between astrocytic swelling and brain pathology is discussed.
Mol Chem Neuropathol 1989 Aug
PMID:Astrocytic swelling in traumatic-hypoxic brain injury. Beneficial effects of an inhibitor of anion exchange transport and glutamate uptake in glial cells. 257 May 84

The interaction of rat liver acetyl-CoA carboxylase with a 2',3'-dialdehyde derivative of ATP (oATP) has been studied. The degree of the enzyme inactivation has been found to depend on the oATP concentration and the incubation time. ATP was the only reaction substrate which provided protection from inactivation. Acetyl-CoA did not affect inactivation, while HCO3- accelerated the process. Ki values for oATP in the absence and the presence of HCO3- were 0.35 +/- 0.04 and 0.5 +/- 0.06 mM, and those of the modification constant (k) were 0.11 and 0.26 min-1, respectively. oATP completely inhibited the reaction of [14C]ADP in equilibrium ATP exchange, whereas produced actually no effect on [14C]acetyl-CoA equilibrium with malonyl-CoA exchange. Incorporation of about one equivalent of [3H]oATP per acetyl-CoA carboxylase subunit has been shown. No restoration of the modified enzyme activity has been observed in Tris or beta-mercaptoethanol containing buffers, and treatment with NaB[3H]4 has not led to 3H incorporation. The modification process involves elimination of the triphosphate chain of oATP. The results obtained indicate the affinity character of oATP-mediated modification of acetyl-CoA carboxylase. The reagent apparently interacts selectively with the epsilon-amino group of lysine in the ATP-binding site to form a morpholine-like structure.
Mol Biol (Mosk)
PMID:[Acetyl-CoA-carboxylase: modification of ATP-binding site of the active center by 2',3'-dialdehyde derivative of ATP]. 257 82


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