| 10563585 |
Androctonin, a novel antimicrobial peptide from scorpion Androctonus australis: solution structure and molecular dynamics simulations in the presence of a lipid monolayer |
10.1080/07391102.1999.10508368. |
J Biomol Struct Dyn |
Androctonin, a novel antimicrobial peptide from scorpion Androctonus australis: solution structure and molecular dynamics simulations in the presence of a lipid monolayer
Abstract
- Androctonin is a highly cationic antimicrobial peptide from scorpion exhibiting a broad spectrum of activities against bacteria and fungi. It contains 25 amino acids including four cysteine residues forming two disulfide bridges. We report here on the determination of its solution structure by conventional two-dimensional (2D) 1H-NMR spectroscopy and molecular modelling using distance geometry and molecular dynamics methods. The structure of androctonin involves a well-defined highly twisted anti-parallel beta-sheet with strands connected by a more variable positively charged turn. A comparison with the structure of tachyplesin I (horseshoe crab) reveals that the amphiphilic character of the protein surface of this homologous peptide is not observed in androctonin. We have undertaken a 200-ps molecular dynamics simulation study on a system including one androctonin molecule and a monolayer of DMPG (1,2-dimyristoylphosphatidylglycerol) lipids. On the basis of this simulation, the first steps of the membrane permeabilization process are discussed.
|
| 10564642 |
Mussel defensins are synthesised and processed in granulocytes then released into the plasma after bacterial challenge |
10.1242/jcs.112.23.4233. |
J Cell Sci |
Mussel defensins are synthesised and processed in granulocytes then released into the plasma after bacterial challenge
Abstract
- MGD1 (Mytilus galloprovincialis defensin 1), a new member of the arthropod defensin family, is a 4 kDa antibacterial peptide previously isolated from the plasma of Mediterranean mussels. We report here the presence of MGD1 in the organelle-rich fraction of hemocytes and the cDNA sequence corresponding to MGD1 and one new isoform mRNA: MGD2. Sequence analysis indicated that MGDs are synthesised as precursors consisting of a putative signal peptide of 21 residues, the active peptide of 39 amino acids and a 21 residue carboxyl-terminal extension, rich in acidic amino acids. Localisation of the transcripts by northern blot revealed that the precursors are abundantly expressed in hemocytes. Immunocytochemistry at both the optical and ultrastructural levels showed that defensins (i) are predominantly located in vesicles of a granulocyte subclass of hemocytes containing small granules, (ii) are also found in large clear granules of another granulocyte subclass, and (iii) that MGD immune reactivity existed in granular structures of enterocytes. Finally, we revealed that bacterial challenge triggered a plasmatic increase of MGD1 concentration and gave evidence of the simultaneous release of the peptides from the hemocytes.
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| 10566018 |
IB 367 |
10.2165/00126839-199901020-00015. |
Drugs R D |
IB 367
Abstract
|
| 10569926 |
Solution structure of carnobacteriocin B2 and implications for structure-activity relationships among type IIa bacteriocins from lactic acid bacteria |
10.1021/bi991351x. |
Biochemistry |
Solution structure of carnobacteriocin B2 and implications for structure-activity relationships among type IIa bacteriocins from lactic acid bacteria
Abstract
- Carnobacteriocin B2 (CbnB2), a type IIa bacteriocin, is a 48 residue antimicrobial peptide from the lactic acid bacterium Carnobacterium pisicola LV17B. Type IIa bacteriocins have a conserved YGNGVXC sequence near the N-terminus and usually contain a disulfide bridge. CbnB2 seemed to be unique in that its two cysteines (Cys9 and Cys14) could be isolated as free thiols [Quadri et al. (1994) J. Biol. Chem. 26, 12204-12211]. To establish the structural consequences of the presence or absence of a disulfide bridge and to investigate if the YGNGVXC sequence is a receptor-binding motif [Fleury et al. (1996) J. Biol. Chem. 271, 14421-14429], the three-dimensional solution structure of CbnB2 was determined by two-dimensional (1)H nuclear magnetic resonance (NMR) techniques. Mass spectroscopic and thiol modification experiments on CbnB2 and on model peptides, in conjunction with activity measurements, were used to verify the redox status of CbnB2. The results show that CbnB2 readily forms a disulfide bond and that this peptide has full antimicrobial activity. NMR results indicate that CbnB2 in trifluoroethanol (TFE) has a well-defined central helical structure (residues 18-39) but a disordered N terminus. Comparison of the CbnB2 structure with the refined solution structure of leucocin A (LeuA), another type IIa bacteriocin, indicates that the central helical structure is conserved between the two peptides despite differences in sequence but that the N-terminal structure (a proposed receptor binding site) is not. This is unexpected because LeuA and CbnB2 exhibit >66% sequence identity in the first 24 residues. This suggests that the N-terminus, which had been proposed [Fleury et al. (1996) J. Biol. Chem. 271, 14421-14429] to be a receptor binding site of type IIa bacteriocins, may not be directly involved and that recognition of the amphiphilic helical portion is the critical feature.
|
| 10570950 |
A novel calcitonin receptor gene in human osteoclasts from normal bone marrow. |
10.1016/s0014-5793(99)01176-x |
FEBS Lett. |
A novel calcitonin receptor gene in human osteoclasts from normal bone marrow.
Abstract
- The calcitonin receptor (CTR) gene in human osteoclasts formed in a human bone marrow cell culture system was examined by reverse transcription-polymerase chain reaction (RT-PCR). The RT-PCR
Results indicated that the 5'-untranslated region (5'UTR) was different between CTR mRNAs in human osteoclasts and in a mammary tumor cell line, MCF-7 cells. We isolated the 5'UTR of the CTR gene from human osteoclasts, whose sequence had only 28.6% identity with that of other CTR genes reported until now. In a radioligand binding assay, COS-1 cells transfected with the osteoclast CTR gene bound to [125I]human CT (hCT). These
Results provided evidence that the CTR gene cloned from human osteoclasts was expressed functionally and its coding protein was identical to MCF-7 cell CTR.
|
| 10572140 |
Genes of the sbo-alb locus of Bacillus subtilis are required for production of the antilisterial bacteriocin subtilosin |
10.1128/JB.181.23.7346-7355.1999. |
J Bacteriol |
Genes of the sbo-alb locus of Bacillus subtilis are required for production of the antilisterial bacteriocin subtilosin
Abstract
- Bacillus subtilis JH642 and a wild strain of B. subtilis called 22a both produce an antilisterial peptide that can be purified by anion-exchange and gel filtration chromatography. Amino acid analysis confirmed that the substance was the cyclic bacteriocin subtilosin. A mutant defective in production of the substance was isolated from a plasmid gene disruption library. The plasmid insertion conferring the antilisterial-peptide-negative phenotype was located in a seven-gene operon (alb, for antilisterial bacteriocin) residing immediately downstream from the sbo gene, which encodes the precursor of subtilosin. An insertion mutation in the sbo gene also conferred loss of antilisterial activity. Comparison of the presubtilosin and mature subtilosin sequences suggested that certain residues undergo unusual posttranslational modifications unlike those occurring during the synthesis of class I (lantibiotic) or some class II bacteriocins. The putative products of the genes of the operon identified show similarities to peptidases and transport proteins that may function in processing and export. Two alb gene products resemble proteins that function in pyrroloquinoline qui biosynthesis. The use of lacZ-alb and lacZ-sbo gene fusions, along with primer extension analysis, revealed that the sbo-alb genes are transcribed from a major promoter, residing upstream of sbo, that is very likely utilized by the sigma(A) form of RNA polymerase. The sbo and alb genes are negatively regulated by the global transition state regulator AbrB and are also under positive autoregulation that is not mediated by the subtilosin peptide but instead requires one or more of the alb gene products.
|
| 10576292 |
Structural studies of atom-specific anticancer drugs acting on DNA |
10.1016/s0163-7258(99)00020-0. |
Pharmacol Ther |
Structural studies of atom-specific anticancer drugs acting on DNA
Abstract
- The interactions of many important anticancer drugs with DNA play important roles in their biological functions. In fact, DNA can be considered as a macromolecular receptor for those drugs. There are several classes of DNA-acting anticancer drugs. Some form noncovalent complexes with DNA by either intercalation (such as daunorubicin and doxorubicin) or groove-binding (such as distamycin A). Others, such as cisplatin, mitomycin C, and ecteinascidins, form covalent linkages with DNA. Finally, some (e.g., duocarmycin/CC-1065, bleomycin/pepleomycin, and enediyne antibiotics) cause DNA backbone cleavages. During the past decade, the detailed molecular interactions of several DNA-acting anticancer drugs with DNA have been studied with structural tools, including high resolution X-ray diffraction and NMR spectroscopy. These results have provided useful insights into DNA conformation and drug-DNA interactions. In particular, it was found that specific atomic sites on DNA are often the targets for drug covalent actions. Here we review the structural aspects of the interactions of several anticancer drugs acting on: (1) the N2 amino group of guanine in the minor groove, (2) the N3 atom of guanine and adenine in the minor groove, (3) the N7 atom of guanine and adenine in the major groove, and finally, (4) the C4', C5', and C1' atoms of the deoxyribose in the backbone of B-DNA double-helix. Understanding the underlying mechanism of the drug action at the cellular and molecular levels through those structural studies should be useful in the development of new anticancer drugs.
|
| 10578151 |
Evidence that somatostatin sst2 receptors mediate striatal dopamine release |
10.1038/sj.bjp.0702934. |
Br J Pharmacol |
Evidence that somatostatin sst2 receptors mediate striatal dopamine release
Abstract
- 1 Somatostatin (SRIF) is a cyclic tetradecapeptide present in medium-sized aspiny interneurones in the rat striatum. We have previously shown that exogenous SRIF potently stimulates striatal dopamine (DA) release via a glutamate-dependent mechanism. We now report the ability of the selective sst2 receptor agonist, BIM-23027, to mimic this effect of SRIF. 2 In vivo microdialysis studies were performed in anaesthetized male Wistar rats. In most experiments, compounds were administered by retrodialysis into the striatum for 15 min periods, 90 min and 225 min after sampling commenced, with levels of neurotransmitters being measured by HPLC with electrochemical and fluorescence detection. 3 BIM-23027 (50 and 100 nM) stimulated DA release with extracellular levels increasing by up to 18 fold. 4 Prior retrodialysis of BIM-23027 (50 nM) abolished the effects of subsequent administration of SRIF (100 nM). 5 The agonist effects of both BIM-23027 and SRIF were abolished by the selective sst2 receptor antagonist, L-Tyr8-CYN-154806 (100 nM). 6 The AMPA/kainate receptor antagonist, DNQX (100 microM), abolished the agonist effects of BIM-23027 as previously shown for SRIF. 7 This study provides evidence that the sst2 receptor mediates the potent dopamine-releasing actions observed with SRIF in the rat striatum. Dopamine release evoked by both peptides appears to be mediated indirectly via a glutamatergic pathway. Other subtype-specific somatostatin receptor ligands were unable to elicit any effects and therefore we conclude that no other somatostatin receptor types are involved in mediating the dopamine-releasing actions of SRIF in the striatum.
|
| 10579905 |
The IGF-I receptor in cancer research. |
10.1006/excr.1999.4667 |
Exp. Cell Res. |
The IGF-I receptor in cancer research.
Abstract
- The type 1 insulin-like growth factor receptor (IGF-IR) plays an important role in both normal and abnormal growth. It is particularly important in anchorage-independent growth. Impairment of its function causes apoptosis of tumor cells and inhibition of tumor growth in experimental animals. However, the IGF-IR can also induce differentiation, and eventually cell death, of certain types of cells. Its major substrates, IRS-1 and Shc, determine whether the IGF-IR will transform cells or will cause their differentiation.
|
| 10581734 |
Correlation of actinomycin X2 to the lipid profile in static and shaken cultures of Streptomyces nasri strain YG62 |
None |
Microbios |
Correlation of actinomycin X2 to the lipid profile in static and shaken cultures of Streptomyces nasri strain YG62
Abstract
- Streptomyces nasri strain YG62 produces a broad-spectrum antibiotic designated actinomycin X2. The influence of static and shaken incubation on the production of actinomycin X2 and lipid profiles of S. nasri strain YG62 was investigated. It was found that shaken incubation was superior to the static process for both actinomycin X2 (2-fold) and total lipids (1.6-fold). Triglyceride and phospholipid levels paralleled the actinomycin X2 production with an increase in the triglyceride (2.8-fold) and phospholipid (1.2-fold) concentrations in the shaken culture over the static incubation. Analysis of fatty acid patterns revealed the occurrence of a wide range of fatty acids (C10-C22). The mean percentage of total saturated fatty acids in shaken culture was higher than those of the static culture. The mean percentage of mono-unsaturated fatty acids was almost the same in both cultures. The mean percentage of the total polyunsaturated fatty acids in the static culture was slightly higher than that of the shaken culture. The polyunsaturated/saturated fatty acid ratio (P/S) was higher in the static culture compared with the shaken culture. A positive correlation was recorded between triglycerides, phospholipids and actinomycin X2. A negative correlation on the other hand, was found between fatty acids and actinomycin X2.
|
| 10591208 |
The DNA sequence of human chromosome 22. |
10.1038/990031 |
Nature |
The DNA sequence of human chromosome 22.
Abstract
- Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
|
| 10599497 |
[Novel endogenous dipeptide cycloprolyl-glycine is similar to pyracetam in selectivity of their mnemotropic effect] |
None |
Biull Eksp Biol Med |
[Novel endogenous dipeptide cycloprolyl-glycine is similar to pyracetam in selectivity of their mnemotropic effect]
Abstract
|
| 10600388 |
Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif |
10.1006/jmbi.1999.3383. |
J Mol Biol |
Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif
Abstract
- Several macrocyclic peptides ( approximately 30 amino acids), with diverse biological activities, have been isolated from the Rubiaceae and Violaceae plant families over recent years. We have significantly expanded the range of known macrocyclic peptides with the discovery of 16 novel peptides from extracts of Viola hederaceae, Viola odorata and Oldenlandia affinis. The Viola plants had not previously been examined for these peptides and thus represent novel species in which these unusual macrocyclic peptides are produced. Further, we have determined the three-dimensional structure of one of these novel peptides, cycloviolacin O1, using (1)H NMR spectroscopy. The structure consists of a distorted triple-stranded beta-sheet and a cystine-knot arrangement of the disulfide bonds. This structure is similar to kalata B1 and circulin A, the only two macrocyclic peptides for which a structure was available, suggesting that despite the sequence variation throughout the peptides they form a family in which the overall fold is conserved. We refer to these peptides as the cyclotide family and their embedded topology as the cyclic cystine knot (CCK) motif. The unique cyclic and knotted nature of these molecules makes them a fascinating example of topologically complex proteins. Examination of the sequences reveals they can be separated into two subfamilies, one of which tends to contain a larger number of positively charged residues and has a bracelet-like circularization of the backbone. The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip. Here we define the structural features of the two apparent subfamilies of the CCK peptides which may be significant for the likely defense related role of these peptides within plants.
|
| 10608807 |
Extensive post-translational modification, including serine to D-alanine conversion, in the two-component lantibiotic, lacticin 3147 |
10.1074/jbc.274.53.37544. |
J Biol Chem |
Extensive post-translational modification, including serine to D-alanine conversion, in the two-component lantibiotic, lacticin 3147
Abstract
- Lacticin 3147 is a two-component bacteriocin produced by Lactococcus lactis subspecies lactis DPC3147. In order to further characterize the biochemical nature of the bacteriocin, both peptides were isolated which together are responsible for the antimicrobial activity. The first, LtnA1, is a 3,322 Da 30-amino acid peptide and the second component, LtnA2, is a 29-amino acid peptide with a mass of 2,847 Da. Conventional amino acid analysis revealed that both peptides contain the thioether amino acid, lanthionine, as well as an excess of alanine to that predicted from the genetic sequence of the peptides. Chiral phase gas chromatography coupled with mass spectrometry of amino acid composition indicated that both LtnA1 and LtnA2 contain D-alanine residues and amino acid sequence analysis of LtnA1 confirmed that the D-alanine results from post-translational modification of a serine residue in the primary translation product. Taken together, these results demonstrate that lacticin 3147 is a novel, two-component, D-alanine containing lantibiotic that undergoes extensive post-translational modification which may account for its potent antimicrobial activity against a wide range of Gram-positive bacteria.
|
| 10609089 |
Distribution of the amatoxins and phallotoxins in Amanita phalloides. Influence of the tissues and the collection site |
10.1016/s0764-4469(00)86651-2. |
C R Acad Sci III |
Distribution of the amatoxins and phallotoxins in Amanita phalloides. Influence of the tissues and the collection site
Abstract
- The toxin composition of 25 Amanita phalloides carpophores collected from three sites in Franche-Comté (France) differing in their geological and pedological characteristics was determined and the factors involved in the variations of the toxin concentration in the tissues were identified. The concentrations of the main amatoxins (beta-amanitin, alpha-amanitin, gamma-amanitin) and phallotoxins (phallacidin, phallisacin, phalloidin, phallisin, phalloin) in the six tissues constituting the carpophore, i.e. the cap (C), gills (G), ring (R), stipe (S), bulb (B) and volva (V) were evaluated by using high-performance liquid chromatography. The results analysed statistically showed that the toxin concentrations were tissue dependent, leading to classification of the tissues into two groups (B, V) and (C, G, R, S). The (B, V) group was distinguished by high amounts of phalloidin, phallisin and phallisacin, and the (C, G, R, S) group by the predominance of the amatoxins. The characteristics of the soil of the collection site also affected the toxin concentrations; however, this effect differed from one site to another and was not similar for all the tissues. Finally, the mean toxin profile in the carpophores from the three sites was evaluated. This study underscores the fact that environmental factors and mainly the soil type clearly have an effect on the toxin composition of A. phalloides carpophores.
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