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Query: UNIPROT:P06889 (Mol)
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Proton NMR spectra of serine proteases in 1H2O solutions typically show a single resonance at very low magnetic field--i.e., 14-18 ppm from dimethylsilylapentanesulfonate. This resonance has been assigned to the proton hydrogen bonded between aspartic acid-102 and histidine-57 (chymotrypsin numbering system) of the "charge-relay system" or catalytic triad of serine proteases [Robillard, G. & Shulman, R. G. (1972) J. Mol. Biol. 71, 507-511]. Since then, there have been a number of reports that have cast doubt on its correctness. In the present work we have tested this assignment using alpha-lytic protease (EC 3.4.21.12, Myxobacter alpha-lytic proteinase), a bacterial serine protease homologous to elastase, which is specifically labeled with nitrogen-15 at N delta 1 of its single histidine residue. The low-field region of the proton spectra of this labeled enzyme shows a single resonance having the properties reported [Robillard, G. & Shulman, R. G. (1974) J. Mol. Biol. 86, 519-540], which, in addition, exhibits spin-spin splitting to the nitrogen-15 label. The observation of this 15N delta 1-H coupling makes the assignment of this resonance to the charge-relay proton unequivocal.
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PMID:Confirmation of the assignment of the low-field proton resonance of serine proteases by using specifically nitrogen-15 labeled enzyme. 393 65

To examine in detail a class of peptides that inhibit the polymerization of deoxyhemoglobin S, we assayed the L-amino acids and 22 dipeptides for their effect on deoxyhemoglobin S solubility. Of the amino acids, the aromatics (phenylalanine, tyrosine, and tryptophan) significantly increased deoxyhemoglobin S solubility, as did high concentration of arginine. Combinations of the hydrophobic (specifically the aromatic) amino acids with a hydrophilic amino acid, such as arginine or lysine, resulted in dipeptides which were much more soluble than the hydrophobic or aromatic amino acid alone, and also inhibited polymerization. Furthermore, samples of deoxyhemoglobin S at 26 to 27 g/dl containing some of these dipeptides such as Arg-Trp, Arg-Phe, and Lys-Trp in excess of 50 to 100 mM did not polymerize, indicating a 1.4- to 1.6-fold increase in deoxyhemoglobin S solubility. The enhancement of polymerization, i.e., decrease in deoxyhemoglobin S solubility, observed by the addition of aspartic acid, glycine, or lysine was observed or was reduced in the dipeptides containing these hydrophilic amino acids combined with hydrophobic amino acids (valine, leucine, isoleucine, or the aromatic amino acids). The effects of these dipeptides on deoxyhemoglobin S solubility were mostly linear with concentration. However, the changes in deoxyhemoglobin S solubility by addition of a dipeptide was not simply the sum of the effects observed with the individual amino acids as exemplified by the differential effect of reversing the dipeptide sequence (e.g., Arg-Phe and Phe-Arg, or Arg-Tyr and Tyr-Arg). These data provide further evidence as to the stereospecific nature of this class of noncovalent inhibitors of deoxyhemoglobin S polymerization.
Mol Pharmacol 1985 Jul
PMID:Dipeptides as inhibitors of the gelation of sickle hemoglobin. 402 96

There are more than 20 beta-actin-specific sequences in the human genome, many of which are pseudogenes. To facilitate the isolation of potentially functional beta-actin genes, we used the new method of B. Seed (Nucleic Acids Res. 11:2427-2446, 1983) for selecting genomic clones by homologous recombination. A derivative of the pi VX miniplasmid, pi AN7 beta 1, was constructed by insertion of the 600-base-pair 3' untranslated region of the beta-actin mRNA expressed in human fibroblasts. Five clones containing beta-actin sequences were selected from an amplified human fetal gene library by homologous recombination between library phage and the miniplasmid. One of these clones contained a complete beta-actin gene with a coding sequence identical to that determined for the mRNA of human fibroblasts. A DNA fragment consisting of mostly intervening sequences from this gene was then used to identify 13 independent recombinant copies of the analogous gene from two specially constructed gene libraries, each containing one of the two types of mutant beta-actin genes found in a line of neoplastic human fibroblasts. The amino acid and nucleotide sequences encoded by the unmutated gene predict that a guanine-to-adenine transition is responsible for the glycine-to-aspartic acid mutation at codon 244 and would also result in the loss of a HaeIII site. Detection of this HaeIII polymorphism among the fibroblast-derived clones verified the identity of the beta-actin gene expressed in human fibroblasts.
Mol Cell Biol 1984 Oct
PMID:Molecular cloning and characterization of mutant and wild-type human beta-actin genes. 609 33

The experiments were carried out to find out whether exogenous glutamic or aspartic acid could diminish changes in the cardiac contractile function and high-energy phosphate content caused by underperfusion of isolated isovolumic rat heart. After 40 min of reduced coronary flow (from 10 to 3 ml/min) there was an almost four-fold fall in the developed pressure, and more than three-fold rise in the diastolic pressure as well as a profound fall in creatine phosphate (CP) and ATP content. Glutamic (68 mM) or aspartic (75 mM) acids were added to the perfusate after 10 min of underperfusion when the developed pressure had declined almost to the same level as was observed after 40 min and the content of CP was reduced more than two-fold. Glutamic acid completely prevented the rise in the diastolic pressure and significantly increased the CP content, as compared to its level observed before addition of glutamate, but glutamic acid did not change the developed pressure. As a result, the CP and ATP contents were three- and two-fold higher, respectively, after addition of glutamic acid as compared to control underperfused hearts. Similar, but slightly less prominent effects were observed when aspartic acid was added instead of glutamic acid. These results suggest that high concentrations of glutamic and aspartic acids can exert beneficial effects on ischemic heart muscle.
J Mol Cell Cardiol 1983 Jan
PMID:Effect of glutamic and aspartic acids on adenine nucleotides, nitrogenous compounds and contractile function during underperfusion of isolated rat heart. 613 4

Beta-2 microglobulin (beta 2M) is a 12,000 dalton protein associated with membrane-bound cell surface antigens. Variants of beta 2M, beta 2MA and beta 2MB, were first detected by Michaelson et al. (Immunogenetics 11, 93-95, 1980). An improved method was used to purify beta 2MA and beta 2MB from BALB/c and C57BL/6 mouse livers, respectively. Reproducible yields of 10% were obtained. The purifications were accomplished by a 3 M sodium thiocyanate (NaSCN) extraction of a crude membrane fraction, an acid precipitation step, gel filtration on Sephadex G-75 and ion-exchange chromatography on DEAE-cellulose and CM-cellulose in that order. The elution profile of beta 2MA and beta 2MB on the ion-exchange columns was found to be different, indicating the presence of structural changes. beta 2MA was found to be more acidic (pI = 7.35) than beta 2MB (pI = 7.68) by isoelectric focusing in gels. Complete sequence analysis of beta 2MA and partial sequence analysis of beta 2MB (61 of 99 residues) were performed by automated Edman degradation of the intact chain and of the overlapping peptides obtained by: (a) tryptic cleavage at arginines after acetimidation of lysine side chains, (b) BNPS-skatole cleavage at tryptophan residues and (c) hydroxylamine cleavage at asparagine-glycine linkages. A comparison of the primary structure of beta 2MA to the partial amino acid sequence obtained for beta 2MB revealed a single amino acid substitution (aspartic acid for alanine at position 85) that accounts for the differences in biochemical properties observed.
Mol Immunol 1982 Mar
PMID:Purification and characterization of mouse beta-2 microglobulin: allelic variants from two different strains. 617 66

This mini-review describes a noval class of excitatory heterocyclic amino acid. The selective interactions of these synthetic amino acids with the central glutamic acid (GLU) and aspartic acid (ASP) receptors have been established on the basis of microelectrophoretic techniques using glutamic acid diethyl ester (GDEE) and alpha-aminoadipic acid (alpha-AA) as selective antagonists for GLU and ASP, respectively. The parent compound, ibotenic acid (IBO) preferentially activates ASP receptors, but elongation of the side chain of IBO afforded homoibotenic acid (homo-IBO), a GLU agonist. The introduction of bulky substituents into the heterocyclic ring of homo-IBO resulted in a dramatic increase in potency. Alteration of the position of the side chain in IBO to give alpha-amino-5-methyl-3-hydroxy-4-isoxazoleacetic acid (AMAA), preserved the ASP agonism. However, elongation of the side chain of AMAA gave alpha-amino-5-methyl-3-hydroxy-4-isoxazolepropionic acid (AMPA), which is a very powerful neuronal excitant with selective interaction with the GLU receptors. None of the new compounds are inhibitors of the binding of 3H-kainic acid (3H-KAIN) to rat brain membranes, indicating that the mechanism of action of these compounds is different from that of the neurotoxic compound KAIN. The described compounds may be important tools in future investigations of the physiological role and the mechanism of action of ASP and GLU in the central nervous system.
Mol Cell Biochem 1981 Aug 11
PMID:Glutamate and aspartate agonists structurally related to ibotenic acid. 627 May 43

The transducing phage lambda dsupM814 and the plasmid pIB1830 containing the wild-type rpoB gene have been constructed and the primary structure of the gene's central fragment has been established. In contrast with the wild-type, the gene of the rpoB255 mutant, whose primary structure has been published, was found to contain an A.T. leads to T.A. transversion entailing the substitution of a valine residue for the aspartic acid residue (516) of the wild-type beta subunit.
Mol Gen Genet 1981
PMID:Primary structure of Escherichia coli RNA polymerase nucleotide substitution in the beta subunit gene of the rifampicin resistant rpoB255 mutant. 627 62

Four actin genes have been isolated from Caenorhabditis elegans that account for all of the major actin hybridization to total genomic DNA. Actin genes I, II and III are clustered within a 12 X 10(3) base region; gene IV is unlinked to the others. All four genes have been sequenced from at least nucleotide -109 to +250. Genes I and III are identical for the first 307 coding nucleotides. Genes I and II differ in 14 positions within the first 250 coding nucleotides; one difference substitutes an aspartic acid for a glutamic acid at codon 5. Genes I and IV differ in 18 positions within the first 259 coding nucleotides without causing any amino acid differences. Genes I, II and III have introns after the first nucleotide of codon 64 and gene IV has an intron between codons 19 and 20. The four nucleotide sequences thus far define two different amino acid sequences. Both of the amino acid sequences resemble vertebrate cytoplasmic actin more than vertebrate muscle actin. A DNA polymorphism between the Bristol and Bergerac strains has been used as a phenotypic marker in genetic crosses to map the cluster of actin genes within a 2% recombination interval on linkage group V between unc-23 and sma-1 in order to begin a molecular genetic analysis of the actin loci.
J Mol Biol 1983 Mar 05
PMID:Actin gene family of Caenorhabditis elegans. 630 75

Two studies on the abiotic formation of amino acids are presented. The first study demonstrates the role of hydrogen cyanide as a precursor of amino acids detected in extracts of lunar samples. The formation of several amino acids, including glycine, alanine, aspartic acid, and glutamic acid, under conditions similar to those used for the analysis of lunar samples is demonstrated. The second study investigates the formation of hydrogen cyanide as well as amino acids from lunar-sample gas mixtures under electrical discharge conditions. These results extend the possibility of synthesis of amino acids to planetary bodies with primordial atmospheres less reducing than a mixture of methane, ammonia, hydrogen and water.
J Mol Evol 1984
PMID:On the abiotic formation of amino acids. I. HCN as a precursor of amino acids detected in extracts of lunar samples. II. Formation of HCN and amino acids from simulated mixtures of gases released from lunar samples. 633 Mar 74

The nature of the cross-reacting groups on two variant surface glycoproteins of Trypanosoma brucei has been investigated after isolation of glycopeptides produced by extensive proteolytic digestion of the proteins. One variant yielded two glycopeptides after pronase digestion, one of which was the glycosylated C-terminal aspartic acid. In a second variant there are two carbohydrate groups close to the C-terminus. Considerable heterogeneity in the size of the sugar attached to an asparagine residue was detected whereas the C-terminal serine was glycosylated but showed no size heterogeneity. For both variants it was shown that the C-terminal glycosylated amino acid (either aspartic acid or serine) was responsible for the immunological cross-reaction between distinct variant glycoproteins. The stability of the cross-reacting determinant was also investigated.
Mol Biochem Parasitol 1983 Apr
PMID:Characterisation of the cross-reacting carbohydrate groups on two variant surface glycoproteins of Trypanosoma brucei. 641 Feb 33


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