Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-04-18DOI: 10.1155/2012/356081
Maurizio Romano, Fabian Feiguin, Emanuele Buratti
{"title":"Drosophila Answers to TDP-43 Proteinopathies.","authors":"Maurizio Romano, Fabian Feiguin, Emanuele Buratti","doi":"10.1155/2012/356081","DOIUrl":"https://doi.org/10.1155/2012/356081","url":null,"abstract":"<p><p>Initially implicated in the pathogenesis of CFTR and HIV-1 transcription, nuclear factor TDP-43 was subsequently found to be involved in the origin and development of several neurodegenerative diseases. In 2006, in fact, it was reported for the first time the cytoplasmic accumulation of TDP-43 in ubiquitin-positive inclusions of ALS and FTLD patients, suggesting the presence of a shared underlying mechanism for these diseases. Today, different animal models of TDP-43 proteinopathies are available in rodents, nematodes, fishes, and flies. Although these models recapitulate several of the pathological features found in patients, the mechanisms underpinning the progressive neuronal loss observed in TDP-43 proteinopathies remain to be characterized. Compared to other models, Drosophila are appealing because they combine the presence of a sophisticated brain with the possibility to investigate quickly and massively phenotypic genetic modifiers as well as possible therapeutic strategies. At present, the development of TDP-43-related Drosophila models has further strengthened the hypothesis that both TDP-43 \"loss-of-function\" and \"gain-of-function\" mechanisms can contribute to disease. The aim of this paper is to describe and compare the results obtained in a series of transgenic and knockout flies, along with the information they have generated, towards a better understanding of the mechanisms underlying TDP-43 proteinopathies.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"356081"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/356081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30610222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Crystal structure of L-histidinium 2-nitrobenzoate.","authors":"Subramanian Natarajan, Kalimuthu Moovendaran, Jeyaperumal Kalyana Sundar, Krishnan Ravikumar","doi":"10.1155/2012/463183","DOIUrl":"https://doi.org/10.1155/2012/463183","url":null,"abstract":"<p><p>A new nonlinear optical organic compound, namely, L-histidinium 2-nitrobenzoate (abbreviated as LH2NB (I); ([C(6)H(10)N(3)O(2)](+) [C(7)H(4)NO(4)](-))), was synthesized. The molecular structure of LH2NB (I) was elucidated using single crystal X-ray diffraction technique. The second harmonic generation (SHG) efficiency of this compound is about two times that of the standard potassium dihydrogen phosphate crystals.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":" ","pages":"463183"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/463183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40184602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-05-14DOI: 10.1155/2012/565404
Charalampos G Pappas, Andreas G Tzakos, Ioannis P Gerothanassis
{"title":"On the hydration state of amino acids and their derivatives at different ionization States: a comparative multinuclear NMR and crystallographic investigation.","authors":"Charalampos G Pappas, Andreas G Tzakos, Ioannis P Gerothanassis","doi":"10.1155/2012/565404","DOIUrl":"10.1155/2012/565404","url":null,"abstract":"<p><p>(2)D, (13)C, (14)N, and (17)O NMR and crystallographic data from the literature were critically evaluated in order to provide a coherent hydration model of amino acids and selected derivatives at different ionization states. (17)O shielding variations, longitudinal relaxation times (T(1)) of (2)D and (13)C and line widths (Δν(1/2)) of (14)N and (17)O, may be interpreted with the hypothesis that the cationic form of amino acids is more hydrated by 1 to 3 molecules of water than the zwitterionic form. Similar behaviour was also observed for N-acetylated derivatives of amino acids. An exhaustive search in crystal structure databases demonstrates the importance of six-membered hydrogen-bonded conjugated rings of both oxygens of the α-carboxylate group with a molecule of water in the vicinity. This type of hydrogen bond mode is absent in the case of the carboxylic groups. Moreover, a considerable number of structures was identified with the propensity to form intramolecular hydrogen bond both in the carboxylic acid (NH⋯O=C) and in the carboxylate (NH ⋯ O(-)) ionization state. In the presence of bound molecules of water this interaction is significantly reduced in the case of the carboxylate group whereas it is statistically negligible in the carboxylic group.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"565404"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30672183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-07-09DOI: 10.1155/2012/691463
Nathaniel G N Milton
{"title":"In Vitro Activities of Kissorphin, a Novel Hexapeptide KiSS-1 Derivative, in Neuronal Cells.","authors":"Nathaniel G N Milton","doi":"10.1155/2012/691463","DOIUrl":"https://doi.org/10.1155/2012/691463","url":null,"abstract":"<p><p>The primary products of the metastasis-suppressor KiSS-1 gene are the kisspeptin (KP) peptides that stimulate gonadotrophin-releasing-hormone (GnRH) release via GPR-54 receptor activation. Recent studies have suggested that the KP-10 peptide also activates neuropeptide FF (NPFF) receptors. The aim of the current study was to determine the activities of the KiSS-1 derivative kissorphin (KSO), which contains the first six amino acids of the KP-10 peptide, is C-terminally amidated, and shares amino acid similarities with the biologically active NPFF 3-8 sequence. The KSO peptide inhibited forskolin-stimulated cyclic adenosine monophosphate (cAMP) production in ND7/23 neuroblastoma cells via an action that could be inhibited by the NPFF receptor antagonist RF9. Release of GnRH by LA-N-1 neuroblastoma cells was not altered by the KSO peptide. In ND7/23 neuroblastoma cells, the KSO peptide was able to reduce forskolin neuroprotection against H(2)O(2) toxicity. The KSO peptide was also able to prevent prostaglandin E2-induced apoptosis in rat cortical neurons. The NPFF receptor antagonist RF9 could inhibit these actions of the KSO peptide in oxidative stress and apoptosis models. In conclusion, the kissorphin peptide, comprising the amino acid sequence Tyr-Asn-Trp-Asn-Ser-Phe-NH(2), has NPFF-like biological activity without showing any GnRH releasing activity and inhibits forskolin-activated cAMP release.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"691463"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/691463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30801999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-12-20DOI: 10.1155/2012/967347
Jyothi Thundimadathil
{"title":"Cancer treatment using peptides: current therapies and future prospects.","authors":"Jyothi Thundimadathil","doi":"10.1155/2012/967347","DOIUrl":"https://doi.org/10.1155/2012/967347","url":null,"abstract":"<p><p>This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"967347"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/967347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31155665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Linkers between Zinc Fingers in Spacing Recognition by Plant TFIIIA-Type Zinc-Finger Proteins.","authors":"Setsuko Fukushima, Michiteru Yoshida, Hiroshi Takatsuji","doi":"10.1155/2012/848037","DOIUrl":"https://doi.org/10.1155/2012/848037","url":null,"abstract":"<p><p>The EPF family of plant TFIIIA-type zinc-finger (ZF) proteins (ZPTs) is characterized by long linkers separating ZF motifs. We previously reported that two-fingered ZPTs bind to two tandem core sites that are separated by several base pairs, each ZF making contact with one core site. Here we report further characterization of DNA-binding activities of ZPTs using four family members, ZPT2-14, ZPT2-7, ZPT2-8, and ZPT2-2, having inter-ZF linkers of different lengths and sequences, to investigate the correlation of the length and/or sequence of the linker with preference for the spacing between core sites in target DNAs. Selected and amplified binding site (SAAB)-imprinting assays and gel mobility shift assays prompted three conclusions. (1) The four ZPTs have common specificity for core binding sites-two AGT(G)/(C)ACTs separated by several nucleotides. (2) The four ZPTs prefer a spacing of 10 bases between the core sites, but each ZPT has its own preference for suboptimal spacing. (3) At a particular spacing, two zinc fingers may bind to the core sites on both strands. The results provide new information about how the diversity in linker length/sequence affects DNA-sequence recognition in this protein family.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":" ","pages":"848037"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/848037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39968469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-03-01DOI: 10.1155/2012/575180
Megan E Schroeder, Heather A Hostetler, Friedhelm Schroeder, Judith M Ball
{"title":"Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides.","authors":"Megan E Schroeder, Heather A Hostetler, Friedhelm Schroeder, Judith M Ball","doi":"10.1155/2012/575180","DOIUrl":"https://doi.org/10.1155/2012/575180","url":null,"abstract":"<p><p>Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol. These interactions indicate that cholesterol/caveolin-1 plays a role in NSP4 transport to the cell surface, which is essential to its enterotoxic activity. Synthetic peptides were utilized to identify target(s) of intervention by exploring the NSP4-caveolin-1 and -cholesterol interactions. NSP4(112-140) that overlaps the caveolin-1 binding domain and a cholesterol recognition amino acid consensus (CRAC) motif and both termini of caveolin-1 (N-caveolin-1(2-20), (19-40) and C-caveolin-1(161-180)) were synthesized. Direct fluorescence-binding assays were employed to determine binding affinities of the NSP4-caveolin-1 peptides and cholesterol. Intracellular cholesterol alteration revealed a redistribution of NSP4 and disintegration of viroplasms. These data further imply interruption of NSP4(112-140)-N-caveolin-1(19-40) and cholesterol interactions may block NSP4 intracellular transport, hence enterotoxicity.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"575180"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/575180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30572143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-01-19DOI: 10.1155/2012/206083
Ilda D'Annessa, Cinzia Tesauro, Paola Fiorani, Giovanni Chillemi, Silvia Castelli, Oscar Vassallo, Giovanni Capranico, Alessandro Desideri
{"title":"Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly-Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin.","authors":"Ilda D'Annessa, Cinzia Tesauro, Paola Fiorani, Giovanni Chillemi, Silvia Castelli, Oscar Vassallo, Giovanni Capranico, Alessandro Desideri","doi":"10.1155/2012/206083","DOIUrl":"https://doi.org/10.1155/2012/206083","url":null,"abstract":"<p><p>Topoisomerases I are ubiquitous enzymes that control DNA topology within the cell. They are the unique target of the antitumor drug camptothecin that selectively recognizes the DNA-topoisomerase covalent complex and reversibly stabilizes it. The biochemical and structural-dynamical properties of the Asp677Gly-Val703Ile double mutant with enhanced CPT sensitivity have been investigated. The mutant displays a lower religation rate of the DNA substrate when compared to the wild-type protein. Analyses of the structural dynamical properties by molecular dynamics simulation show that the mutant has reduced flexibility and an active site partially destructured at the level of the Lys532 residue. These results demonstrate long-range communication mechanism where reduction of the linker flexibility alters the active site geometry with the consequent lowering of the religation rate and increase in drug sensitivity.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"206083"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/206083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30444086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-02-28DOI: 10.1155/2012/736837
Volodymyr I Lushchak
{"title":"Glutathione homeostasis and functions: potential targets for medical interventions.","authors":"Volodymyr I Lushchak","doi":"10.1155/2012/736837","DOIUrl":"https://doi.org/10.1155/2012/736837","url":null,"abstract":"<p><p>Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"736837"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/736837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30572146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Amino AcidsPub Date : 2012-01-01Epub Date: 2012-07-22DOI: 10.1155/2012/735076
Azaria Solomon Eisenberg, Laura J Juszczak
{"title":"Correlation of TrpGly and GlyTrp Rotamer Structure with W7 and W10 UV Resonance Raman Modes and Fluorescence Emission Shifts.","authors":"Azaria Solomon Eisenberg, Laura J Juszczak","doi":"10.1155/2012/735076","DOIUrl":"https://doi.org/10.1155/2012/735076","url":null,"abstract":"<p><p>Tryptophyl glycine (TrpGly) and glycyl tryptophan (GlyTrp) dipeptides at pH 5.5 and pH 9.3 show a pattern of fluorescence emission shifts with the TrpGly zwitterion emission solely blue shifted. This pattern is matched by shifts in the UV resonance Raman (UVRR) W10 band position and the W7 Fermi doublet band ratio. Ab initio calculations show that the 1340 cm(-1) band of the W7 doublet is composed of three modes, two of which determine the W7 band ratios for the dipeptides. Molecular dynamics simulations show that the dipeptides take on two conformations: one with the peptide backbone extended; one with the backbone curled over the indole. The dihedral angle critical to these conformations is χ(1) and takes on three discrete values. Only the TrpGly zwitterion spends an appreciable amount of time in the extended backbone conformation as this is stabilized by two hydrogen bonds with the terminal amine cation. According to a Stark effect model, a positive charge near the pyrrole keeps the (1)L(a) transition at high energy, limiting fluorescence emission red shift, as observed for the TrpGly zwitterion. The hydrogen bond stabilized backbone provides a rationale for the C(methylene)-C(α)-C(carbonyl) W10 symmetric stretch that is unique to the TrpGly zwitterion.</p>","PeriodicalId":14901,"journal":{"name":"Journal of Amino Acids","volume":"2012 ","pages":"735076"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/735076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30830617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}