Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylation at the alpha-amino terminal is a common post-translational modification of many peptides and proteins. In the case of the potent opiate peptide beta-endorphin, alpha-N-acetylation is a known physiological modification that abolishes opiate activity. Since there are no known receptors for alpha-N-acetyl-beta-endorphin, we have studied the association of this peptide with calmodulin, a calcium-dependent protein that binds a variety of peptides, phenothiazines, and enzymes, as a model system for studying acetylated endorphin-protein interactions. Association of the acetylated peptide with calmodulin was demonstrated by cross-linking with bis(sulfosuccinimidyl)suberate; like beta-endorphin, adducts containing 1 mol and 2 mol of acetylated peptide per mole calmodulin were formed. Some of the bound peptides are evidently in relatively close proximity to each other since, in the presence of amidated (i.e., lysine-blocked) calmodulin, cross-linking yielded peptide dimers. The acetylated peptide exhibited no appreciable helicity in aqueous solution, but in trifluoroethanol (TFE) considerable helicity was formed. Also, a mixture of acetylated peptide and calmodulin was characterized by a circular dichroic spectrum indicative of induced helicity. Empirical prediction rules, applied earlier to beta-endorphin, suggest that residues 14-24 exhibit alpha-helix potential. This segment has the potential of forming an amphipathic helix; this structural unit is believed to be important in calmodulin binding. The acetylated peptide was capable of inhibiting the calmodulin-mediated stimulation of cyclic nucleotide phosphodiesterase (EC 3.1.4.17) activity with an effective dose for 50% inhibition of about 3 microM; this inhibitory effect was demonstrated using both an enzyme-enriched preparation as well as highly purified enzyme. Thus, acetylation at the alpha-amino terminal of beta-endorphin, although abolishing opiate activity, does not interfere with the binding to calmodulin. Indeed, beta-endorphin and the alpha-N-acetylated peptide behave very similarly with respect to calmodulin association.
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PMID:Interaction of alpha-N-Acetyl-beta-endorphin and calmodulin. 285 97

The ability of apocytochrome c and the heme containing respiratory chain component, cytochrome c, to induce fusion of phosphatidylcholine (PC) small unilamellar vesicles containing 0-50 mol % negatively charged lipids was examined. Both molecules mediated fusion of phosphatidylserine (PS):PC 1:1 vesicles as measured by energy transfer changes between fluorescent lipid probes in a concentration- and pH-dependent manner, although cytochrome c was less potent and interacted over a more limited pH range than the apocytochrome c. Maximal fusion occurred at pH 3, far below the pKa of the 19 lysine groups contained in the protein (pI = 10.5). A similar pH dependence was observed for vesicles containing 50 mol % cardiolipin (CL), phosphatidylglycerol (PG), and phosphatidylinositol (PI) in PC but the apparent pKa values varied somewhat. In the absence of vesicles, the secondary structure of apocytochrome c was unchanged over this pH range, but in the presence of negatively charged vesicles, the polypeptide underwent a marked conformational change from random coil to alpha-helix. By comparing the pH dependencies of fusion induced by poly-L-lysine and apocytochrome c, we concluded that the pH dependence derived from changes in the net charge on both the vesicles and apocytochrome c. Aggregation could occur under conditions where fusion was imperceptible. Fusion increased with increasing mole ratio of PS. Apocytochrome c did induce some fusion of vesicles composed only of PC with a maximum effect at pH 4. Biosynthesis of cytochrome c involves translocation of apocytochrome c from the cytosol across the outer mitochondrial membrane to the outer mitochondrial space where the heme group is attached. The ability of apocytochrome c to induce fusion of both PS-containing and PC-only vesicles may reflect characteristics of protein/membrane interaction that pertain to its biological translocation.
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PMID:Apocytochrome c induces pH-dependent vesicle fusion. 302 48

A protein which preferentially binds Z-form duplex DNA has been purified from the cells of Deinococcus radiodurans. The molecular weight of the protein was estimated to be approximately 68,000 by gel filtration and SDS-polyacrylamide gel electrophoresis. Amino acid analysis of the protein indicates that it is not so basic since it contains a lower mole percent of lysine and higher mole percent of aspartic acid than those in histone-like DNA binding protein II (HU) of Escherichia coli. The first fifteen amino acid residues from the N-terminus have been also determined.
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PMID:Isolation of a DNA-binding protein from Deinococcus radiodurans having an affinity for a Z-form polynucleotide. 306 34

Phosphoenolpyruvate carboxylase from maize leaves was inactivated by pyridoxal 5'-phosphate in the dark and in the light. A two-step reversible mechanism is proposed for inactivation in the dark, which involves the formation of a noncovalent complex prior to a Schiff base with amino groups of the enzyme. Spectral analysis of pyridoxal 5'-phosphate-modified phosphoenolpyruvate carboxylase showed absorption maxima at 432 and 327 nm, before and after reduction with NaBH4, respectively, suggesting that epsilon-amino groups of lysine residues are the reactive groups in the enzyme. A correlation between spectral data and the maximal inactivation obtained with several concentrations of inhibitor allowed us to establish that the incorporation of 4 mol of pyridoxal 5'-phosphate per mole of holoenzyme accounts for total inactivation. The absence of modifier bound to phosphoenolpyruvate carboxylase when the modification was carried out in the presence of phosphoenolpyruvate and MgCl2 suggests the existence of an essential lysine residue at the catalytic site of the enzyme. Modification of phosphoenolpyruvate carboxylase in the light under an oxygen atmosphere resulted in an irreversible inactivation, which was completely protected by phosphoenolpyruvate and MgCl2. Spectral analysis of the photomodified enzyme showed an absorption peak of 320 nm, suggesting light-mediated addition of a nucleophilic residue (probably an imidazole group) to the pyridoxal 5'-phosphate-lysine azomethine bond.
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PMID:Modification of an essential amino group of phosphoenolpyruvate carboxylase from maize leaves by pyridoxal phosphate and by pyridoxal phosphate-sensitized photooxidation. 308 90

Although the effect of aspirin in blood coagulation has been believed to be due to its ability to interfere with platelet function, very few studies have reported its effect on various blood coagulation proteins. Since aspirin (acetylsalicylic acid) is known to acetylate numerous biologic macromolecules, the effect of aspirin on antithrombin III was investigated. It was found that antithrombin III is irreversibly inactivated by treatment with aspirin. The inactivation follows pseudo first-order kinetics and incorporation of one molecule of aspirin per molecule of the protein is necessary for complete inactivation. Reaction with acetyl-[14C]-salicylic acid incorporated 1.4 mol of acetyl group per mole of protein but reaction with carboxyl-[14C]-acetyl salicylic acid incorporated only 0.03 mol of radioactive label per mole of the protein. Furthermore, sodium salicylate does not inactivate the protein. This suggests that the reaction occurs through the acetylation of antithrombin III. Amino group analysis of aspirin-treated antithrombin III using trinitrobenzenesulfonic acid revealed that one to two primary amino groups are lost relative to the untreated antithrombin III. It is concluded that the reaction of aspirin with antithrombin III results in specific acetylation of lysine residues.
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PMID:Acetylation of antithrombin III by aspirin. 309 26

A lysine-reactive cross-linker has been coupled to the minor base 3-(3-amino-3-carboxypropyl)uridine in the variable loop of the Escherichia coli elongator methionine tRNA (tRNA(mMet]. Incubation of the derivatized tRNA with E. coli methionyl-tRNA synthetase (MetRS) resulted in covalent coupling of the protein and nucleic acid and loss of amino acid acceptor activity of the enzyme. One mole of tRNA was cross-linked per mole of enzyme inactivated. Enzyme activity was largely restored by release of the bound tRNA following cleavage of the disulfide bond in the cross-linker with a sulfhydryl reagent. The cross-linking reaction was effectively inhibited by unmodified tRNA(mMet) but not by noncognate tRNA(Phe). The covalent complex was digested with trypsin, and the resulting tRNA-bound peptides were isolated by anion-exchange chromatography. The cross-linked peptides were released from the tRNA by cleavage in the disulfide bond of the cross-linker and purified by reverse-phase high-pressure liquid chromatography, yielding one major peptide plus several minor peptides. Amino acid analysis indicated that the major product was an octadecapeptide cross-linked to tRNA(mMet) through lysine residue 596 in the primary sequence of MetRS. The N-terminal sequence of the peptide was determined to be Val-Ala-Leu-Ile-Glu-Asn-Ala-Glu-Phe-Val, corresponding to residues 582-591 in MetRS. The procedures described here should be applicable to the determination of peptide sequences near the variable loop of other tRNAs containing the 3-(3-amino-3-carboxypropyl)uracil base when such tRNAs are bound to specific proteins.
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PMID:Covalent coupling of the variable loop of the elongator methionine tRNA to a specific lysine residue in Escherichia coli methionyl-tRNA synthetase. 310 75

The major iron-regulated protein (MIRP) was purified, from both Neisseria gonorrhoeae and N. meningitidis by selective extraction with cetyltrimethylammonium bromide followed by ion-exchange and moleculair-seive chromatography. Solutions of the purified proteins had a characteristic pink color. The overall amino acid composition of these proteins was similar, although differences were noted in the number of serine, threonine, and lysine residues. Nevertheless, the N-terminal amino acid sequence was identical through 47 residues for both the meningococcal and gonococcal MIRP. Plasma emission spectrophotometry revealed that the meningococcal 37K protein contained ca. 1 mole Fe/mole protein.
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PMID:Characterization of the major iron-regulated protein of Neisseria gonorrhoeae and Neisseria meningitidis. 313 Jul 84

Subattomole analysis of fluorescein isothiocyanate (FITC) derivatives of amino acids is accomplished by combining capillary zone electrophoresis for high-efficiency separation with laser-induced fluorescence for high-sensitivity detection. Concentration detection limits range from 5 x 10(-12) molar for alanine to 9 x 10(-11) molar for lysine, injected in the column; 9 x 10(-21) mole of alanine is contained within the approximately 1-nanoliter injection volume at the detection limit. The alanine detection limit corresponds to fewer than 6000 molecules injected onto the column and represents an improvement of four orders of magnitude in the state of the art for fluorescent detection of amino acids and an improvement of six orders of magnitude in the state of the art for the detection limit for isothiocyanate derivatives of amino acids.
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PMID:Subattomole amino acid analysis by capillary zone electrophoresis and laser-induced fluorescence. 314 Mar 81

L-Amino acid oxidase (EC.1.4.3.2) was purified to homogeneity via four steps consisting of Sephadex G-100, CM-Toyopearl 650M, and first and second granulated hydroxyapatite column chromatographies. The mol. wt of the enzyme was 140,000 when estimated by analytical gel filtration and was 70,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the enzyme is composed of two identical subunits. The enzyme has an absorption spectrum characteristic of flavoprotein, contains 2 moles of FMN per mole of enzyme and has an isoelectric point of 5.4. The enzyme oxidatively deaminated hydrophobic amino acids such as Leu, Met, Phe, and Tyr while basic amino acids except for Lys were also oxidized though at slower rates. This specificity was generally similar, with some exceptions, to that of the enzyme from Trimeresurus flavoviridis venom. For oxidative deamination of Leu, Km and maximum velocity of the enzyme were 1.17 mM and 9.9 units/mg, respectively, at pH 7.6. The activity was inhibited almost completely by heavy metal ions, some aromatic benzoates and sulfhydryl reagents but not by metal-chelating agents.
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PMID:Purification and characterization of L-amino acid oxidase from the venom of Trimeresurus mucrosquamatus (Taiwan habu snake). 318 59

Polyglycine, polyalanine, polyleucine, poly-alpha-glutamic acid, poly-gamma-glutamic acid and poly-alpha-lysine were complexed with insulin under non denaturating conditions. The liberation behaviour of the hormone was investigated in vivo and in vitro in dependence of the insulin content, mole mass, ionic interaction and hydrophobicity of the polyamino acid. The in vitro results were mainly confirmed by animal experiments and indicated distinct effects of the physiochemical parameters to the bioavailability of insulin. The complex of poly-alpha-lysine and polyglycine were shown to be the most suited retard form, producing significant blood glucose lowering effects up to 12 hours.
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PMID:[Insulin polyamino acid complexes--a variable principle in the preparation of sustained-release forms]. 329 85


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