Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mixture of iturines extracted from Bacillus subtilis gave, on column chromatography, iturine A, iturine B, and iturine C. Iturine A has the entire antifungal activity. It is a mixture of two homologous peptidolipids C48,H74N12O14 and C49H76N12O14 (mp 177 degrees C, [alpha]D-1.7 degrees in methanol (c 0.05 g/mL); mol wt 1042 and 1056). The lipid moiety is a mixture of 3-amino-12-methyltridecanoic acid and 3-amino-12-methyltetradecanoic acid. The peptide moiety contains 7 mol of amino acids: D-Asn2, L-Asn, L-Gln, L-Pro, L-Ser, and D-Tyr. A cyclic structure for iturine A with the serine residue linked to the fatty amino acids through a peptide bond has been domonstrated. By mild HCl hydrolysis, lipid-soluble and water-soluble peptides were obtained. They were analyzed by chemical methods and by mass spectrometry. Permethylated and perdeuteriomethylated derivatives of iturine A were also subjected to mass spectrometric analysis. Both chemical analysis and mass spectrometry led to the cyclic structure I for iturine A.
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PMID:Structure of iturine A, a peptidolipid antibiotic from Bacillus subtilis. 10 Dec 32

The electrical responses induced by external applications of neutral amino acids were used to determine whether different carriers are expressed in the membrane of embryonic epithelial cells of Xenopus laevis. Competition experiments were performed under voltage-clamp conditions at constant membrane potential. Gly, L-Ala, L-Pro, L-Ser, L-Asn and L-Gln generate electrical responses with similar apparent kinetic constants and compete for the same carrier.They are [Na]o and voltage-dependent, insensitive to variations in [Cl]o and [HCO3]o, inhibited by pHo changes, by amiloride and, for a large fraction of the current, by MeAIB. The increase in [K]o at constant and negative membrane potential reduces the response, whereas lowering [K]o augments it. L-Leu, L-Phe and L-Pro appear to compete for another carrier. They generate electrogenic responses insensitive to amiloride and MeAIB, as well as to alterations of membrane potential, [Na]o and [K]o. Lowering [Cl]o decreases their size, whereas increasing [HCO3]o at neutral pHo increases it. It is concluded that at least two and possibly three transport systems (A, ASC and L) are expressed in the membrane of the embryonic cells studied. An unexpected electrogenic character of the L system is revealed by the present study and seems to be indirectly linked to the transport function. L-Pro seems to be transported by system A or ASC in the presence of Na and by system L in the absence of Na. MeAIB induces an inward current.
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PMID:Electrophysiological investigation of the amino acid carrier selectivity in epithelial cells from Xenopus embryo. 260 Sep 61

The conformation in solution of mycosubtilin, an antifungal lipopeptide [cyclo(L-Asn-D-Tyr-D-Asn-L-Gln-L-Pro-D-Asn-L-Ser-beta-amino acid)]has been probed by two-dimensional nuclear magnetic resonance and restrained energy minimization. Several structures have been proposed belonging to the same family with minor local variations related to different orientations of amide planes. The molecular topology was found to be completely different from that of iturin A, an analogue which exhibits quite different biological properties. The cyclic peptide of mycosubtilin is shown to be rather rigid in the region of L-proline and stabilized by C7 structures; in contrast, the neighbourhood of D-tyrosine-2 was found to be more flexible. The validity of our models is discussed first in terms of distance violation and second on the basis of reconstructed NOE spectroscopy maps. The different limitations towards higher-resolution structures are discussed.
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PMID:Modelling and refinement of the conformation of mycosubtilin in solution from two-dimensional NMR data. 369 98

Peptides containing the tripeptide sequence Arg-Gly-Asp can duplicate or inhibit the cell attachment-promoting effects of fibronectin and vitronectin. Peptides analogous to a prototype peptide, Gly-Arg-Gly-Asp-Ser-Pro-Cys, the sequence of which was taken from the cell attachment site of fibronectin, were assayed for their relative abilities to inhibit the attachment of cells to a fibronectin or vitronectin substrate. A peptide having the L-Arg residue replaced with D-Arg showed no difference in this capacity, whereas substituting Gly with D-Ala or L-Asp with D-Asp resulted in completely inactive peptides. Replacement of L-Ser with D-Ser drastically reduced the influence that the resulting peptide had on the vitronectin interaction, but this peptide showed little difference in its effect on the binding of cells to fibronectin when compared with the prototype peptide. Furthermore, substitution of the Ser with L-Asn resulted in a peptide that had an apparent increased preference for the fibronectin receptor and decreased preference for the vitronectin receptor. Conversely, threonine in this position gave a peptide with increased preference for the vitronectin receptor, whereas L-Pro in this position gave a completely inactive peptide. Finally, by cyclicizing the prototype peptide to restrict its conformational flexibility, a peptide was obtained that was a much improved inhibitor of attachment of cells to vitronectin and yet nearly inactive with respect to the interactions of cells with fibronectin substrates. These studies lend support to the hypothesis that different Arg-Gly-Asp-directed adhesion receptors can recognize differences in the conformation and environment of the Arg-Gly-Asp tripeptide, and they establish the feasibility of obtaining synthetic probes that are more selective for individual receptors than are the peptides modeled after the natural sequences of adhesive extracellular matrix molecules.
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PMID:Influence of stereochemistry of the sequence Arg-Gly-Asp-Xaa on binding specificity in cell adhesion. 369 52

A series of small peptides, such as might arise in the course of intralysosomal protein digestion, were screened for the ability to escape, intact, from mouse peritoneal macrophage lysosomes. Inability to penetrate lysosomal membranes was inferred from a peptide's induction of lysosomal swelling, or vacuolization, in cultured macrophages. Two of the peptides tested, (D-Glu)(2) and (D-Ala)(3), induced vacuolization. Neither peptide was susceptible to hydrolysis by enzymes in macrophages or in the serum-containing culture medium. Their morphological effect was inhibited by parafluorophenylalanine, an inhibitor of pinocytosis. Once formed by either peptide, the vacuoles persisted for several hours in peptide-free medium. Quantitative studies of radioactively labeled (D-Glu)(2) confirmed the morphological evidence that (D-Glu)(2) is taken up by pinocytosis and stored, intact, in macrophage lysosomes. The majority of the peptides which failed to induce vacuolization-(L-Ala)(2), L-Ser.L-Ala, L-Val.L-Ala, L-Ala.L-Thr, Gly.D, L-Phe, L-Ala.D-His, (L-Ala)(3), (L-Glu)(2), and D-Leu.L-Tyr-were found to be susceptible to hydrolysis by cellular or serum peptidases. Their failure to induce vacuolization was attributed to their hydrolysis to subunits capable of penetrating lysosomal membranes. Some of the peptides which had failed to induce vacuolization-(D-Ala)(2), D-Ser.D-Ala, D-Val.D-Ala, Gly-D-Asn, D-Ala.D-Thr, and D-Arg.D-Val-were found to be indigestible. Except for the cytotoxic peptide D-Arg.D-Val, peptides in this category all had lower molecular weights and volumes than (Glu)(2) or (Ala)(3). It is inferred that these peptides are small enough to escape from macrophage lysosomes, while (Glu)(2) and (Ala)(3) are too large to escape intact. The implications of this inference for the mechanism of intracellular digestion of pinocytosed proteins are discussed.
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PMID:The fate of peptides pinocytosed by macrophages in vitro. 578 69

The multi-enzyme system responsible for the biosynthesis of iturin, an antifungal lipopeptide of Bacillus subtilis, was partially purified by chromatography on different affigels. In the wild-type strain, two subunits of the iturin synthetase (ITs and ITagp) were characterized: ITs activated only L-Ser, one of the iturin amino acid components, and ITagp activated L-Asn, D-Asn, L-Gln and L-Pro, amino acids corresponding to a partial sequence of iturin. In an iturin deficient mutant, the activity of the ITagp subunit was modified.
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PMID:Characterization of iturin synthetase in the wild-type Bacillus subtilis strain producing iturin and in an iturin deficient mutant. 886 95

A21978C and A54145 are antibacterial 13-residue peptides with a medium-chain-acylated amino terminus and a 10-residue lactone ring; they are produced by strains of Streptomyces roseosporus and Streptomyces fradiae, respectively. The structural differences in their peptide chains, which include amino acid replacements and modifications (L-Glu2-->L-Asn, L-Asn(OH)3-->L-Asp, Sar5-->Gly, L-Ala6-->L-Orn, L-Lys8-->D-Ala, L-Asp(OMe)9-->L-Asp, L-Asn11-->D-Ser, and L-lle13-->L-Kyn; Sar = sarcosine; L-Orn = L-ornithine, L-Kyn = L-kynurenine), reside in the multienzymatic templates directing their biosynthesis. We have examined the peptide synthetases employing immunodetection and substrate activation detected by the amino-acid-dependent ATP-PP1-exchange reaction. Two different antibodies specific for actinomycin synthetase 2 and a peptide sequence characteristic of acyl-CoA-synthetases/peptide synthetases were applied. For the A21978 system two peptide synthetases of 670 and 240 kDa were detected, together with two similar proteins of 630 and 440 kDa occurring in varying amounts. The latter are suggested to be degradation products of an unstable multienzyme. Activation of L-Asp, L-Thr, Gly, L-Orn, L-Ala and L-Ser were assigned to the high-molecular-mass components of 670, 630 and 440 kDa. The 240-kDa protein was purified to homogeneity and shown to catalyse activation of L-kynurenine. The A54145 system consisted of three peptide synthetases of 690, 590 and 250 kDa. Activations of L-Asn. L-Thr and Gly were found. The 250-kDa synthetase was capable of activating isoleucine and valine. Both systems thus show a comparable organisation; implications for the modular construction of their peptide synthetases are discussed.
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PMID:Biosynthesis of acylpeptidolactones of the daptomycin type. A comparative analysis of peptide synthetases forming A21978C and A54145. 902 95

The effects of amino acids on growth hormone (GH) release and cytosolic calcium concentration ([Ca2+]i) were investigated in caprine anterior pituitary cells cultured for 3 d in Dulbecco modified Eagle medium. The addition of an amino acid mixture consisting of seven nonessential amino acids (NEAA: L-Asp, Gly, L-Ala, L-Ser, L-Pro, L-Asn, and L-Glu; concentration of each 12.5-200 mumol/l) in the medium significantly raised GH release from the cultured cells in a concentration-dependent manner with the maximum release at 200 mumol/l NEAA. Although an addition of L-Asp (0.1-100 mumol/l) caused a significant rise in GH release in a concentration-dependent manner, neither the individual amino acids contained in NEAA except L-Asp nor others (L-Leu, L-Phe, L-Gln, L-Met, and L-Arg) caused a rise in GH release when added alone to the medium. The rise in GH release induced by NEAA (200 mumol/l) and GH-releasing hormone (GHRH, 10 nmol/l) was significantly reduced by the addition of EGTA (1.8 mmol/l) and nifedipine (1 mumol/l) to the medium, respectively. The addition of NEAA (200 mumol/l) caused a rapid and transient [Ca2+]i increase, followed thereafter by a steady increase. The prior addition of nifedipine (1 mumol/l), which itself significantly reduced the basal [Ca2+]i, completely abolished the response induced by NEAA or GHRH. From these findings, we conclude that: 1) NEAA raises GH release and [Ca2+]i in cultured caprine anterior pituitary cells, and 2) Ca2+ influx from the medium may be responsible for the cellular action of NEAA.
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PMID:Growth hormone release induced by an amino acid mixture from primary cultured anterior pituitary cells of goats. 906 52

In order to improve the high-performance liquid chromatographic separation of alpha-amino acids derivatized with the fluorogenic reagent 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) on commercially available chiral stationary phases (CSPs) such as SUMICHIRAL OA-2500(S) (CSP 1) and OA-4700 (CSP 3), the preparation of two new CSPs (CSP 2 and CSP 4) having 11-aminoundecanoic acid between the aminopropyl silica gel support and the chiral moiety in CSP 1 and CSP 3 is described. CSP 2 and CSP 4 improved both the mutual and enantiomeric separation of NBD-amino acids compared with CSP 1 and CSP 3. Thus, 17 pairs of NBD-amino acid enantiomers and NBD-glycine were separated on CSP 2 except for six NBD-amino acids (D-Asn, D-Ser, D-Gln, L-Pro, L-Ser and Gly). CSP 2 and CSP 4 also showed better enantiomeric separation of NBD-amino acid esters and amides than CSP 1 and CSP 3. It was considered that the achiral long alkyl chains in the CSPs might form a hydrophobic space which assisted the stereoselective interaction of analytes with the chiral moiety by changing the environment around the chiral moiety. On CSP 1 and CSP 2, NBD-beta-amino acid was also enantiomerically separated.
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PMID:Preparation and evaluation of new Pirkle type chiral stationary phases with long alkyl chains for the separation of amino acid enantiomers derivatized with NBD-F. 1043 50

Bacillus subtilis RB14 is a producer of the antifungal lipopeptide iturin A. Using a transposon, we identified and cloned the iturin A synthetase operon of RB14, and the sequence of this operon was also determined. The iturin A operon spans a region that is more than 38 kb long and is composed of four open reading frames, ituD, ituA, ituB, and ituC. The ituD gene encodes a putative malonyl coenzyme A transacylase, whose disruption results in a specific deficiency in iturin A production. The second gene, ituA, encodes a 449-kDa protein that has three functional modules homologous to fatty acid synthetase, amino acid transferase, and peptide synthetase. The third gene, ituB, and the fourth gene, ituC, encode 609- and 297-kDa peptide synthetases that harbor four and two amino acid modules, respectively. Mycosubtilin, which is produced by B. subtilis ATCC 6633, has almost the same structure as iturin A, but the amino acids at positions 6 and 7 in the mycosubtilin sequence are D-Ser-->L-Asn, while in iturin A these amino acids are inverted (i.e., D-Asn-->L-Ser). Comparison of the amino acid sequences encoded by the iturin A operon and the mycosubtilin operon revealed that ituD, ituA, and ituB have high levels of homology to the counterpart genes fenF (79%), mycA (79%), and mycB (79%), respectively. Although the overall level of homology of the amino acid sequences encoded by ituC and mycC, the counterpart of ituC, is relatively low (64%), which indicates that there is a difference in the amino acid sequences of the two lipopeptides, the levels of homology between the putative serine adenylation domains and between the asparagine adenylation domains in the two synthetases are high (79 and 80%, respectively), implying that there is an intragenic domain change in the synthetases. The fact that the flanking sequence of the iturin A synthetase coding region was highly homologous to the flanking sequence that of xynD of B. subtilis 168 and the fact that the promoter of the iturin A operon which we identified was also conserved in an upstream sequence of xynD imply that horizontal transfer of this operon occurred. When the promoter was replaced by the repU promoter of the plasmid pUB110 replication protein, production of iturin A increased threefold.
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PMID:Cloning, sequencing, and characterization of the iturin A operon. 1159 69


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