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)

An enzyme was purified 163-fold in an 8.2% yield from bovine kidney. The specific activities of the pure preparation against L-prolyl glycylglycine and L-alanyl glycylglycine were found to be 244.5 and 578 micron Moles substrate hydrolyzed per min per mg protein respectively. The molecular weight of the enzyme was estimated on gel filtration to be 55,000. The isoelectric point was recorded to be pH 5.2. A preliminary study of substrate specificity showed that the enzyme preferentially hydrolyzed tripeptides of the type X-glycylglycine. The enzyme was tentatively identified as a tripeptide aminopeptidase (alpha aminoacyldipeptide hydrolase, EC 3.4.11.4).
Mol Cell Biochem 1979 Jan 15
PMID:Purification and partial characterisation of a bovine kidney aminotripeptidase (capable of cleaving prolyl-glycylglycine). 42 94

Alayl, [ 14c]-alanyl, phenylalanyl, and methionyl adenylates have been synthesized in high yields and relatively good purities. Elemental analysis 1H nmr and ir spectra have been utilized for the characterization of these extremely labile compounds. The present synthesis, which uses readily available N-tert-butoxycarbonyl amino acids, is compared with previous methods.
J Mol Evol 1979 Jul 18
PMID:Synthesis of amino acyl adenylates using the tert-butoxycarbonyl protecting group. 48 Mar 68

Theoretical studies on glycyl-alanyl and seryl dipeptides were performed to determine the probable backbone and side-group conformations that are preferred for solvent interaction. By following the method of Lee & Richards [(1971) J. Mol. Biol. 55, 379-400], a solute molecule is represented by a set of interlocking spheres of appropriate van der Waals radii assigned to each atom, and a solvent (water) molecule is rolled along the envelope of the van der Waals surface, and the surface accessible to the solvent molecule, and hence the solvent accessibility for a particular conformation of the solute molecule, is computed. From the calculated solvent accessibilities for various conformations, solvation maps for dipeptides were constructed. These solvation maps suggest that the backbone polar atoms could interact with solvent molecules selectively, depending on the backbone conformation. A conformation in the right-handed bridge (zetaR) region is favoured for both solvent interaction and intrachain hydrogen-bonding. Also the backbone side-chain hydrogen-bonding within the same dipeptide fragment in proteins is less favoured than hydrogen-bonding between side chain and water and between side chain and atoms of other residues. Solvent accessibilities suggest that very short distorted alphaR-helical and extended-structural parts may be stabilized via solvent interaction, and this could easily be possible at the surface of the protein molecules, in agreement with protein-crystal data.
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PMID:Solvent accessibilities in glycyl, alanyl and seryl dipeptides. 58 49

The affinity of an antibody for its ligand 2-phenyloxazolone was improved by protein design. For the design two-dimensional nuclear magnetic resonance spectroscopy, protein engineering and molecular modelling were used in an interactive scheme. Initially the binding site was localized with the help of transferred nuclear Overhauser enhancement signals from two, site specifically assigned tyrosine side-chains in the complementarity-determining regions of the antibody to the ligand 4-glycyl-2-phenyloxazolone. On their basis the hapten was placed into a model of the Fv-fragment built according to the principles of canonical antibody structures. From the model, unfavourable contacts between hapten and an aspartyl side-chain in complementarity-determining region 3 of the heavy chain were predicted. Substitution of the aspartyl residue by alanine resulted in a threefold increase in affinity of the antibody Fv-fragment for two hapten derivatives when compared with the wild-type. Nuclear magnetic resonance analysis of the improved Fv-fragment revealed an interaction between the alpha-carbon proton of alanyl residue with the ligand, which was not seen for the aspartyl residue. This interaction is not entirely in accordance with the model, which predicts an interaction between the side-chain of this residue and the hapten. However, it shows that by combined use of nuclear magnetic resonance analysis and molecular modelling, a residue that is critical for antigen binding was identified, whose mutation allowed the design of an improved antibody combining site.
J Mol Biol 1992 Apr 20
PMID:Improving the antigen affinity of an antibody Fv-fragment by protein design. 156 79

Histidyl dipeptides such as carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-amino-butyryl-L-histidine) are reported at millimolar concentrations in several mammalian tissues (O'Dowd et al., 1988; House et al., 1989), but their precise physiological function, or functions, is uncertain. These compounds are known to be potent buffers at physiological pH (Davey, 1960). They are also able to restore functional capacity to fatigued muscle preparations, stimulate some glycolytic enzymes and maintain coupling between mitochondrial oxidation and phosphorylation (Severin, 1964). Histidyl dipeptides may also have antioxidant activity, though this finding is controversial. For example, Aruoma et al. have argued that these compounds, individually, are unable to scavenge superoxide (O2-.), hydrogen peroxide (H2O2) or hypochlorous acid (HOCl) at rates which could offer antioxidant protection in vivo. Since there is a range of these histidyl dipeptides within mammalian tissue we have investigated possible synergism between them in respect of antioxidant activity. Our results show that combining histidine-containing compounds at near physiological concentrations results in synergistic antioxidant activity.
J Mol Cell Cardiol 1991 Nov
PMID:Synergism of histidyl dipeptides as antioxidants. 180 15

We have used 125I-labeled fibronectin (FN) as an extracellular substrate for neutrophils (PMN) in order to investigate the mechanism responsible for FN solubilization by PMN and the effects of recombinant cytokines on this process. Pure active alpha 1-antitrypsin (alpha 1AT), when added to PMN before or during, but not after, adherence to FN, inhibited solubilization of the substrate in a dose-dependent manner, but alpha 1AT that had been inactivated by proteolysis or oxidation and alpha 1AT Pittsburgh (alpha 1AT 358Met-Arg) had no significant effect. The solubilization of FN was also inhibited by the PMN elastase inhibitor N-methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethylketone but not by the chymotrypsin and cathepsin G inhibitor N-Cbz-glycyl-glycyl-phenylalanine-chloromethylketone, nor by catalase or superoxide dismutase. The products of solubilization of FN by PMN, analyzed by sodium dodecyl sulphate polyacrylamide electrophoresis, were similar to those produced by pure PMN elastase but not cathepsin G. These results suggest that FN solubilization by PMN is caused largely by the pericellular activity of PMN elastase. The solubilization of FN by PMN was increased significantly by adding tumor necrosis factor-alpha, interleukin-1 alpha, or interferon-gamma to the adherent cells but without a significant general release of elastase into the culture supernatants. Granulocyte/macrophage colony-stimulating factor (GM-CSF) had no significant effect. None of the cytokines had any effect when preincubated with the cells in suspension, and non increased FN solubilization by PMN incubated with the optimal (10(-6) mol/liter) or suboptimal dose (10(-8) mol/liter) of the peptide formylmethionylleucylphenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Apr
PMID:Extracellular proteolysis of fibronectin by neutrophils: characterization and the effects of recombinant cytokines. 201 99

The histidine-containing phosphocarrier protein (HPr) from Bacillus subtilis has been crystallized. Two of the site-directed mutants aimed at probing function produce crystals suitable for X-ray studies. The mutant in which His15 is substituted by an alanyl residue crystallizes from ammonium sulfate solution in space group P3(1)21 or P3(2)21, with unit cell dimensions: a = b = 47.3 A; c = 61.5 A. These crystals diffract to at least 1.8 A resolution. The mutant in which Ser46 is substituted by an aspartyl residue crystallizes from polyethylene glycol 4000 solution in space group P2(1), with unit cell dimensions: a = 49.4 A; b = 25.6 A; c = 60.3 A; beta = 109 degrees. These crystals diffract to at least 2.0 A resolution.
J Mol Biol 1990 Mar 05
PMID:Crystallization of the Bacillus subtilis histidine-containing phosphocarrier protein HPr and of some of its site-directed mutants. 210 49

Although X-ray crystallographic and NMR studies have been made on the adenylate kinases, the substrate-binding sites are not unequivocally established. In an attempt to shed light on the binding sites for MgATP2- and for AMP2- in human cytosolic adenylate kinase (EC 2.7.4.3, hAK1), we have investigated the enzymic effects of replacement of the arginine residues (R44, R132, R138, and R149), which had been assumed by Pai et al. [Pai, E. F., Sachsenheimer, W., Schirmer, R. H., & Schulz, G. E. (1977) J. Mol. Biol. 114, 37-45] to interact with the phosphoryl groups of AMP2- and MgATP2-. With use of the site-directed mutagenesis method, point mutations were made in the artificial gene for hAK1 [Kim, H. J., Nishikawa, S., Tanaka, T., Uesugi, S., Takenaka, H., Hamada, M., & Kuby, S. A. (1989) Protein Eng. 2, 379-386] to replace these arginine residues with alanyl residues and yield the mutants R44A hAK1, R132A hAK1, R138A hAK1, and R149A hAK1. The resulting large increases in the Km,app values for AMP2- of the mutant enzymes, the relatively small increases in the Km,app values for MgATP2-, and the fact that the R132A, R138A, and R149A mutant enzymes proved to be very poor catalysts are consistent with the idea that the assigned substrate binding sites of Pai et al. (1977) have been reversed and that their ATP-binding site may be assigned as the AMP site.
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PMID:In vitro mutagenesis studies at the arginine residues of adenylate kinase. A revised binding site for AMP in the X-ray-deduced model. 215 84

An elastase-specific fluorogenic substrate, 6-(N-carbo-benzoxy-L-alanyl-L-alanyl-L-alanylamido)-qu inoline, was synthesized and immobilized via the fluorophoric group to an alkylatable derivative of polyacrylamide microspheres. Upon hydrolysis by elastase, the proteolytic product of the reaction fluorescences with a characteristic greenish-yellow light corresponding to the presence of the 1-alkyl-6-aminoquinolinium ion. This method has been applied to detect the elastase activity released from monocytes grown on the microspheres. Because the fluorescent product is covalently attached to the microsphere and cannot diffuse away from the site of reaction, it is possible to identify individual cells releasing the proteinase molecules. These experiments demonstrate that covalently immobilized fluorogenic substrates can be used for direct visualization and quantitation of proteinase activity from individual cells in culture.
Cell Mol Biol 1989
PMID:Immobilized fluorogenic substrates for proteinases: a method for visualization and quantitation of elastase release from human monocytes. 261 31

The self-assembly properties of the arginine 8-vasopressin/bovine neurophysin II (AVP/BNPII) biosynthetic precursor were studied using glycopeptide-deleted and sequence-redesigned semisynthetic derivatives. Semisynthetic precursors were prepared by chemically coupling synthetic vasopressinyl sequence domains and native protein-derived neurophysin II domain. Measurement of precursor-protein association by the extent of affinity chromatographic retardation on agarose-immobilized BNPII verified that the semisynthetic precursor with native AVP sequence has an enhanced self-association propensity similar to that predicted for native precursor. Here, the stabilizing contacts between hormone and neurophysin domains, mainly the positively charged protonated alpha-amino group and tyrosyl 2 side chain of the hormone, are retained. Semisynthetic precursor variants in which the hormone domain is sequence-simplified by introducing alanyl residues in positions not considered important for neurophysin recognition show non-reduced association to BNPII. In contrast, removal of one of the main contact elements between hormone and neurophysin by acetylation of the hormone alpha-amino group abolishes potentiation of precursor self-association. The results show that the presence of the C-terminal glycopeptide sequence domain of native vasopressin precursor is not required to promote self-assembly of the precursor. The data verify the view proposed for the oxytocinyl precursor that intramolecular domain interaction is the triggering event which promotes the increase in affinity of precursor self-association (intermolecular self-recognition). The data also define some of the intramolecular self-recognition elements in the folded precursor required for the high affinity intermolecular self-recognition.
J Mol Recognit 1989 Apr
PMID:Sequence simplification and the intra- and intermolecular self-recognition properties of vasopressin/neurophysin biosynthetic precursor. 263 63


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