SEARCH · Search PubMed

Results for “ASPARTIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1997

D-aspartic acid localization during postnatal development of rat adrenal gland.

Developmental changes in cellular localization of D-aspartic acid (D-Asp) were investigated in rat adrenal gland with polyclonal anti-D-Asp antibody. At 1 and 3 weeks of age, immunoreactivity (IR) toward this amino acid was intense in the cytoplasm of cells in the zona fasciculata (ZF) and zona reticularis (ZR) of the adrenal cortex but was less so in the zona glomerulosa (ZG). Conversely at 8 weeks of age, intense IR was observed in the ZG and less in the ZF and ZR. In the adrenal medulla, IR was evident in large clusters of cells which were identified as adrenaline-storing cells. The emergence of D-Asp in specific types of cells at distinct periods of development of rat adrenal gland suggests that this amino acid may have a physiological role in the maturation of the organ.

Adrenal Cortex↗

PubMed1980

Bidirectional synthesis of [5-aspartic acid] arginine vasopressin on poly-N-acrylylpyrrolidine resin.

In the proposed biologically active conformation of vasopressin at its antidiuretic receptor, the side-chain carboxamide moiety of the 5-position asparaginyl residue has been suggested to be an active element for the initiation of the antidiuretic response. [5-Aspartic acid] arginine vasopressin, the analog in which the -NH2 portion of the primary amide has been replaced by an -OH group, has been synthesized and tested for some of the pharmacological activities of vasopressin. The partially protected nonapeptide intermediate was assembled bidirectionally on a poly-N-acrylylpyrrolidine resin. The 6-position cysteinyl residue was attached to the resin via its side-chain through an S-carbamoyl linkage. First the COOH-terminus was extended by coupling with Pro-Arg(Tos)-Gly-NH2, then the NH2-terminus was extended in a stepwise manner. [5-Aspartic acid] arginine vasopressin was found to possess 86.5 +/- 4.8 units/mg of antidiuretic potency, 17% of the parent hormone. In addition, the analog possesses rat pressor and rat uterotonic potencies of 6.93 +/- 0.15 and 0.38 +/- 0.03 units/mg, respectively. This result suggests that a carboxylic acid moiety on the 5-position aspartyl residue retains sufficient steric features and hydrophilicity in common with the carboxamide moiety present in the hormone to substitute for it as an active element at the antidiuretic receptor.

Acrylic Resins↗

PubMed1969

Hemoglobin Yoshizuka (G10(108)beta asparagine--aspartic acid): a new variant with a reduced oxygen affinity from a Japanese family.

During the course of a survey, a new hemoglobin, designated hemoglobin Yoshizuka, has been encountered in a Japanese family. Clinically, mild anemia was noted in five of six heterozygous individuals but no other significant abnormalities were found. Hemoglobin Yoshizuka is characterized by the substitution of aspartic acid for asparagine at the tenth residue of the G helix in the beta-chain. Reduced oxygen affinity with almost normal heme-heme interaction was found to be a property of this abnormal hemoglobin. The asparagine residue G10(108)beta lies in the internal cavity of the tetrameric molecule and its main chain carbonyl is thought to be hydrogen bonded to histidine G10(103)alpha at the region of contact between alpha- and beta-chains. It would appear likely that the introduction of a carboxyl group into the central cavity might result in interactions between the polar groups and the substituted side chain, disrupting the system of hydrogen bonds which contribute to the stability of the contacts between unlike subunits.

Amino Acids↗

PubMed1987

Determination of 4-aminobutyric acid, aspartate, glutamate and glutamine and their 13C stable-isotopic enrichment in brain tissue by gas chromatography-mass spectrometry.

A selected-ion monitoring method was developed for measuring 4-aminobutyric acid, aspartate, glutamate, and glutamine in brain tissue. Natural isotopes of these amino acids and their stable-isotopic enrichment following intravenous infusion of a precursor, [13C]glucose, were quantitated. Frozen mouse brain tissue was homogenized in cold 80% ethanol, and the supernatant, equivalent to 1 mg of wet weight brain tissue, was extracted using solid-phase bonded silica ion-exchange columns. Aspartate and glutamate (dicarboxylic acids) were isolated from strong anion-exchange columns, whereas 4-aminobutyric acid and glutamine (neutral amino acids) were isolated from strong-cation exchange columns. n-Butyl ester pentafluoropropionyl amide derivatives of these amino acids were analyzed by gas chromatography-mass spectrometry using a methane positive chemical ionization mode after gas chromatographic separation on a wide-bore, fused-silica capillary column. The method is applicable to determination of brain concentrations of these amino acids as well as their fluxes following administration of a stable-isotopic tracer.

Amino Acids↗

PubMed2001

The role for an invariant aspartic acid in hypoxanthine phosphoribosyltransferases is examined using saturation mutagenesis, functional analysis, and X-ray crystallography.

The role of an invariant aspartic acid (Asp137) in hypoxanthine phosphoribosyltransferases (HPRTs) was examined by site-directed and saturation mutagenesis, functional analysis, and X-ray crystallography using the HPRT from Trypanosoma cruzi. Alanine substitution (D137A) resulted in a 30-fold decrease of k(cat), suggesting that Asp137 participates in catalysis. Saturation mutagenesis was used to generate a library of mutant HPRTs with random substitutions at position 137, and active enzymes were identified by complementation of a bacterial purine auxotroph. Functional analyses of the mutants, including determination of steady-state kinetic parameters and pH-rate dependence, indicate that glutamic acid or glutamine can replace the wild-type aspartate. However, the catalytic efficiency and pH-rate profile for the structural isosteric mutant, D137N, were similar to the D137A mutant. Crystal structures of four of the mutant enzymes were determined in ternary complex with substrate ligands. Structures of the D137E and D137Q mutants reveal potential hydrogen bonds, utilizing several bound water molecules in addition to protein atoms, that position these side chains within hydrogen bond distance of the bound purine analogue, similar in position to the aspartate in the wild-type structure. The crystal structure of the D137N mutant demonstrates that the Asn137 side chain does not form interactions with the purine substrate but instead forms novel interactions that cause the side chain to adopt a nonfunctional rotamer. The results from these structural and functional analyses demonstrate that HPRTs do not require a general base at position 137 for catalysis. Instead, hydrogen bonding sufficiently stabilizes the developing partial positive charge at the N7-atom of the purine substrate in the transition-state to promote catalysis.

Alanine↗

PubMed1987

Structural analysis of the temperature-sensitive mutant of bacteriophage T4 lysozyme, glycine 156----aspartic acid.

The structure of the mutant of bacteriophage T4 lysozyme in which Gly-156 is replaced by aspartic acid is described. The lysozyme was isolated by screening for temperature-sensitive mutants and has a melting temperature at pH 6.5 that is 6.1 degrees C lower than wild type. The mutant structure is destabilized, in part, because Gly-156 has conformational angles (phi, psi) that are not optimal for a residue with a beta-carbon. High resolution crystallographic refinement of the mutant structure (R = 17.7% at 1.7 A resolution) shows that the Gly----Asp substitution does not significantly alter the configurational angles (phi, psi) but forces the backbone to move, as a whole, approximately 0.6 A away from its position in wild-type lysozyme. This induced strain weakens a hydrogen bond network that exists in the wild-type structure and also contributes to the reduced stability of the mutant lysozyme. The introduction of an acidic side chain reduces the overall charge on the molecule and thereby tends to increase the stability of the mutant structure relative to wild type. However, at neutral pH this generalized electrostatic stabilization is offset by specific electrostatic repulsion between Asp-156 and Asp-92. The activity of the mutant lysozyme is approximately 50% that of wild-type lysozyme. This reduction in activity might be due to introduction of a negative charge and/or perturbation of the surface of the molecule in the region that is assumed to interact with peptidoglycan substrates.

Aspartic Acid↗

PubMedDate not supplied

Application of aspartic acid racemization to forensic odontology: post mortem designation of age at death.

The extent of racemization of aspartic acid in the dentin of healthy, carious and impacted teeth was used to define the ages of individuals at the time of their death. These determinations were performed with an error of +/- 4 years. This method holds the promise of simplifying procedures in, and extending the application of forensic odontology. The current error range of this method may be reduced by analyzing teeth of the same positional types from deceased individuals of known age. Using this method, it appears that post mortem preservation of up to 10 years has a negligible effect on the values determined for the age of individuals at death.

Adolescent↗

PubMed1985

Degeneration of cholinergic neurons in the basal nucleus following kainic or N-methyl-D-aspartic acid application to the cerebral cortex in the rat.

The effect on cholinergic neurons in the basal nucleus of exposing the cortex to excitotoxic amino acids was examined in the rat. Kainic or N-methyl-D-aspartic acid were applied extradurally over the cerebral cortex of one side. This resulted in a severe depletion in the numbers of neurons in the underlying cortex. The immunohistochemically identified cholinergic neurons of the ipsilateral basal nucleus showed a significant shrinkage, -31% of their mean cell area, which was comparable with the retrograde degeneration seen following direct mechanical damage of the cortex. These findings suggest that cholinergic neurons of the basal nucleus can undergo transneuronal retrograde degeneration.

Animals↗

PubMed1999

Determination of aspartic acid enantiomers in bio-samples by capillary electrophoresis.

Enantiomeric separation and detection of D,L-aspartic acid (Asp) derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) by capillary electrophoresis (CE) using modified cyclodextrins as chiral selectors was studied. Heptakis(2,3, 6-tri-O-methyl)-beta-cyclodextrin(TM-beta-CD) was most effective for enantiomeric separation of NBD-D,L-Asp with optimum conditions of 30 mM TM-beta-CD in 50 mM phosphate buffer (pH 4.0) and the limit of detection (LOD) attained was 100 nM for each enantiomer. The method proposed in the present study was convenient for both D- and L-Asp determination since the other amino compounds migrated differently and D-Asp in bio-samples such as rat pineal gland and foods was determined with a simple sample pretreatment and a short analysis run time.

Animal Feed↗

PubMed1993

Bacillus cohnii sp. nov., a new, obligately alkaliphilic, oval-spore-forming Bacillus species with ornithine and aspartic acid instead of diaminopimelic acid in the cell wall.

A group of 20 alkaliphilic Bacillus strains in which all strains revealed the same unique comination of properties--obligate alkaliphily, oval spores distending the sporangium, and ornithine and aspartic acid instead of diaminopimelic acid in the cell wall--was examined. Most of the strains had been isolated by a five-step enrichment and isolation procedure. The G+C content was determined to span a range from 33.5 to 35.0 mol%. Unsaturated fatty acids amounted to 17 to 28% of the total cellular fatty acids. Through DNA-DNA hybridization experiments 11 strains could be grouped in one species. Low homology values with the type strains of validly published Bacillus species with similar G+C contents suggest that these strains belong to a hitherto undescribed species for which the name Bacillus cohnii is proposed. The type strain of the new species is strain RSH (= DSM 6307).

Amino Acid Sequence↗

PubMed2003

Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein.

The secreted Mac protein made by serotype M1 group A Streptococcus (GAS) (designated Mac(5005)) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils. This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG). Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity. Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity. Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level. The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein. These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac.

Amino Acid Sequence↗

PubMed1993

Identification of N,N'-dicyclohexylcarbodiimide-reactive glutamic and aspartic acid residues in Escherichia coli transhydrogenase and the exchange of these by site-specific mutagenesis.

Pyridine nucleotide transhydrogenase (EC 1.6.1.1) from Escherichia coli was investigated with respect to the role of glutamic and aspartic acid residues reactive to N,N'-dicyclohexylcarbodiimide (DCCD) and potentially involved in the proton-pumping mechanism of the enzyme. The E. coli transhydrogenase consists of an alpha (510 residues) and a beta (462 residues) subunit. DCCD reacts with the enzyme to inhibit catalytic activity and proton pumping. This reagent modifies Asp alpha 232, Glu alpha 238, and Glu alpha 240 as well as amino acid residue(s) in the beta subunit. Using the cloned and overexpressed E. coli transhydrogenase genes (Clarke, D. M., and Bragg, P. D. (1985) J. Bacteriol. 162, 367-373), Asp alpha 232 and Glu alpha 238 were replaced independently by site-specific mutagenesis. In addition, Asp alpha 232, Glu alpha 238, and Glu alpha 240 were replaced to generate triple mutants. The specific catalytic activities of the mutant transhydrogenases alpha D232N, alpha D232E, alpha D232K, alpha D232H, alpha E238K, and alpha E238Q as well as of the triple mutants alpha D232N, alpha E238Q, alpha E240Q and alpha D232H, alpha E238Q, alpha E240Q were in the range of 40-90% of the wild-type activity. Proton-pumping activity was present in all mutants. Examination of the extent of subunit modification by [14C]DCCD revealed that the label was still incorporated into both alpha and beta subunits in the Asp alpha 232 mutants, but that the alpha subunit was not labeled in the triple mutants. Catalytic and proton-pumping activities were nearly insensitive to DCCD in the triple mutants. This suggests that loss of catalytic and proton-pumping activities is associated with modification of the aspartic and glutamic acid residues of the alpha subunit. In the presence of the substrate NADPH, the rate of modification of the beta subunit by [14C]DCCD was increased, and there was a greater extent of enzyme inactivation. By contrast, NADH and 3-acetylpyridine-NAD+ protected the catalytic activity of the transhydrogenase from inhibition by DCCD. The protection was particularly marked in the E238Q and E238K mutants. It is concluded that the Asp alpha 232, Glu alpha 238, and Glu alpha 240 residues are not essential for catalytic activity or proton pumping. The inactivation by DCCD is likely due to the introduction of a sterically hindering group that reacts with the identified acidic residues close to the NAD(H)-binding site.

Amino Acid Sequence↗

PubMed2001

Facile synthesis of (R)-4-mercaptopyrrolidine-2-thione from L-aspartic acid.

An SN2-type of substitution of (S)-bromide 4, which had been prepared from L-aspartic acid, with potassium thiobenzoate provided (R)-benzoylthio derivative 5 with complete inversion of the configuration. Compound 5 was converted, via iodide 6c, to (R)-4-amino-3-benzoylthiobutyric acid 8b. (R)-4-Mercapto pyrrolidine-2-thione 1 was readily obtained from 8b through cyclization with acetic anhydride, thionation with Lawesson's reagent and facile removal of the S-benzoyl group with sodium methoxide.

Aspartic Acid↗

PubMed2003

A highly conserved aspartic acid residue in the signature disulfide loop of the alpha 1 subunit is a determinant of gating in the glycine receptor.

Ligand-gated ion channels (LGICs) mediate rapid chemical neurotransmission. This gene superfamily includes the nicotinic acetylcholine, GABAA/C, 5-hydroxytryptamine type 3, and glycine receptors. A signature disulfide loop (Cys loop) in the extracellular domain is a structural motif common to all LGIC member subunits. Here we report that a highly conserved aspartic acid residue within the Cys loop at position 148 (Asp-148) of the glycine receptor alpha1 subunit is critical in the process of receptor activation. Mutation of this acidic residue to the basic amino acid lysine produces a large decrease in the potency of glycine, produces a decrease in the Hill slope, and converts taurine from a full agonist to a partial agonist; these data are consistent with a molecular defect in the receptor gating mechanism. Additional mutation of Asp-148 shows that alterations in the EC50 for agonists are dependent upon the charge of the side chain at this position and not molecular volume, polarity, or hydropathy. This study implicates negative charge at position Asp-148 as a critical component of the process in which agonist binding is coupled to channel gating. This finding adds to an emerging body of evidence supporting the involvement of the Cys loop in the gating mechanism of the LGICs.

Amino Acid Motifs↗

PubMed2006

The TadV protein of Actinobacillus actinomycetemcomitans is a novel aspartic acid prepilin peptidase required for maturation of the Flp1 pilin and TadE and TadF pseudopilins.

The tad locus of Actinobacillus actinomycetemcomitans encodes genes for the biogenesis of Flp pili, which allow the bacterium to adhere tenaciously to surfaces and form strong biofilms. Although tad (tight adherence) loci are widespread among bacterial and archaeal species, very little is known about the functions of the individual components of the Tad secretion apparatus. Here we characterize the mechanism by which the pre-Flp1 prepilin is processed to the mature pilus subunit. We demonstrate that the tadV gene encodes a prepilin peptidase that is both necessary and sufficient for proteolytic maturation of Flp1. TadV was also found to be required for maturation of the TadE and TadF pilin-like proteins, which we term pseudopilins. Using site-directed mutagenesis, we show that processing of pre-Flp1, pre-TadE, and pre-TadF is required for biofilm formation. Mutation of a highly conserved glutamic acid residue at position +5 of Flp1, relative to the cleavage site, resulted in a processed pilin that was blocked in assembly. In contrast, identical mutations in TadE or TadF had no effect on biofilm formation, indicating that the mechanisms by which Flp1 pilin and the pseudopilins function are distinct. We also determined that two conserved aspartic acid residues in TadV are critical for function of the prepilin peptidase. Together, our results indicate that the A. actinomycetemcomitans TadV protein is a member of a novel subclass of nonmethylating aspartic acid prepilin peptidases.

Aggregatibacter actinomycetemcomitans↗

PubMed2001

Spectroscopic and electrochemical investigation of ternary complexes of D- or L-aspartic acid containing polyacrylamides-Cu(2+)-bovine serum albumin and their radio-stability.

D- or L-aspartic acid containing polyacrylamides were synthesized. Binary and ternary complex formation between these polymers with copper and bovine serum albumin was studied by spectroscopic and electrochemical measurement. Depending on the ratio of the polymer/copper and protein/polymer, the mixture exhibited water-soluble and insoluble character. A hypothetical structural scheme for the formation of ternary complexes is proposed. The effect of radiation on these complexes was also investigated.

Acrylic Resins↗

PubMed1993

Racemization of aspartic acid in the extracellular matrix proteins of primary and secondary dentin.

The accumulation with age of D-aspartic acid in primary and secondary human dentin was determined. In primary dentin, the plot of the D/L Asp ratio vs. age was found to fit first-order kinetics in accordance with the literature. But the secondary dentin behaved in an irregular manner and showed, in the great majority of cases, significantly increased D/L Asp ratios. Possible reasons for these findings, such as differences in protein composition and/or in the prevailing temperature, are discussed.

Adolescent↗

PubMed1981

1H NMR studies on interactions of calcium and magnesium with aspartic acid and asparagine.

1H NMR was used to establish the modes of binding magnesium and calcium ions with L-aspartic acid and L-asparagine. Constants of vicinal proton-proton coupling were used to evaluate the rotational isomerism of amino acids and and their complexes with metal ions. Both ions studied interact with carboxyl groups of amino acids but only magnesium ion binds with amino group.

Animals↗