1,343,150 research outputs found
Theoretical implications of a pre-erythrocytic Plasmodium vivax vaccine for preventing relapses
Preventing malaria infection through vaccination requires preventing every sporozoite inoculated by mosquito bite: a major challenge for Plasmodium falciparum. Plasmodium vivax sporozoites consist of tachysporozoites causing primary infection and bradysporozoites leading to relapses.We hypothesise that a candidate P. vivax vaccine with low efficacy against primary infection may substantially reduce transmission by preventing relapses
Dizajniranje i sinteza novih derivata tiofenkarbohidrazida, tienopirazola i tienopirimidina s antioksidativnim i antitumorskim djelovanjem
2-Amino-5-acetyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (1) and 5-acetyl-2-amino-4-methylthiophene-3-carbohydrazide (2) were synthesized and used as starting materials for the synthesis of new series of 1-(5-amino-4-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3a), 1-(5-amino-4-(4-chloro-3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3b), 1-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) pyrazolidine-3,5-dione (4), (Z)-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) formohydrazonic acid (5a), (Z)-ethyl-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonylformo hydrazonate (5b), 6-acetyl-3-amino-2,5-dimethylthieno2,3-dpyrimidin-4(3H)-one (8), 5-methyl-3-amino-2-mercapto-6-acetylthieno2,3-dpyrimidin-4(3H)-one (10) and 5-methyl-6-acetyl-2-thioxo-2,3-dihydrothieno2,3-dpyrimidin-4(1H)-one (12) as potential antioxidant and antitumor agents. Pharmacological results showed that compounds 6a, 6b, 8, 10 and 12 exhibited promising antitumor and antioxidant activity.Etilni ester 2-amino-5-acetil-4-metil-tiofen-3-karboksilne kiseline (1) i 5-acetil-2-amino-4-metiltiofen-3-karbohidrazid (2) sintetizirani su i upotrebljeni kao reaktanti u sintezi novih spojeva 1-(5-amino-4-(3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3a), 1-(5-amino-4-(4-klor-3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3b), 1-(4-metil-2-amino-5-acetiltiofen-3-karbonil) pirazolidin-3,5-diona (4), (Z)-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonil) formohidrazonske kiseline (5a), (Z)-etil-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonilformo hidrazonata (5b), 6-acetil-3-amino-2,5-dimetiltieno2,3-dpirimidin-4(3H)-one (8), 5-metil-3-amino-2-merkapto-6-acetiltieno2,3-dpirimidin-4(3H)-ona (10) i 5-metil-6-acetil-2-tiokso-2,3-dihidrotieno2,3-dpirimidin-4(1H)-ona (12) kao potencijalnih antioksidansa i citostatika. Farmakološka ispitivanja ukazuju na to da spojevi 6a, 6b, 8, 10 i 12 imaju značajno antitumorsko i antioksidativno djelovanje
Distances and classification of amino acids for different protein secondary structures
Window profiles of amino acids in protein sequences are taken as a
description of the amino acid environment. The relative entropy or
Kullback-Leibler distance derived from profiles is used as a measure of
dissimilarity for comparison of amino acids and secondary structure
conformations. Distance matrices of amino acid pairs at different conformations
are obtained, which display a non-negligible dependence of amino acid
similarity on conformations. Based on the conformation specific distances
clustering analysis for amino acids is conducted.Comment: 15 pages, 8 figure
Impaired nutrient signaling and body weight control in a Na⁺ neutral amino acid cotransporter (Slc6a19)-deficient mouse
Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of
epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0)
amino acid transporter BᴼAT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na⁺ -dependent uptake of neutral amino acids into the intestine and renal brush-border
membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters
was detected. Mice lacking BᴼAT1 showed a reduced body weight. When adapted to a standard 20% protein diet, BᴼAT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response
pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid
uptake is essential for optimal growth and body weight regulation.This work was supported by National Health and Medical Research Council Grant 525415, Australian Research Council Grant DP0877897, University of Sydney Bridging Grant RIMS2009-02579), and by an anonymous
foundatio
Structure, Organization, and Expression of the lct Gene for Lacticin 481, a Novel Lantibiotic Produced by Lactococcus lactis
The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 61-residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in β-methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry.
A thermodynamic basis for prebiotic amino acid synthesis and the nature of the first genetic code
Of the twenty amino acids used in proteins, ten were formed in Miller's
atmospheric discharge experiments. The two other major proposed sources of
prebiotic amino acid synthesis include formation in hydrothermal vents and
delivery to Earth via meteorites. We combine observational and experimental
data of amino acid frequencies formed by these diverse mechanisms and show
that, regardless of the source, these ten early amino acids can be ranked in
order of decreasing abundance in prebiotic contexts. This order can be
predicted by thermodynamics. The relative abundances of the early amino acids
were most likely reflected in the composition of the first proteins at the time
the genetic code originated. The remaining amino acids were incorporated into
proteins after pathways for their biochemical synthesis evolved. This is
consistent with theories of the evolution of the genetic code by stepwise
addition of new amino acids. These are hints that key aspects of early
biochemistry may be universal.Comment: 16 pages, 2 tables, 4 figures. Accepted for publication in
Astrobiolog
Is Amino-Acid Homochirality Due To Asymmetric Photolysis In Space?
Amino acids occurring in proteins are, with rare exceptions, exclusively of
the L-configuration. Among the many scenarios put forward to explain the origin
of this chiral homogeneity (i.e., homochirality), one involves the asymmetric
photolysis of amino acids present in space, triggered by circularly polarized
UV radiation. The recent observation of circularly polarized light (CPL) in the
Orion OMC-1 star-forming region (Bailey et al. 1998, Science 281, 672) has been
presented as providing a strong validation of this scenario. The present paper
reviews the situation. It is stressed for example that one important condition
for the asymmetric photolysis by CPL to be at the origin of the terrestrial
homochirality of natural amino acids is generally overlooked, namely, the
asymmetric photolysis should favour the L-enantiomer for ALL the primordial
amino acids involved in the genesis of life (i.e., biogenic amino acids).
Although this condition is probably satisfied for aliphatic amino acids, some
non-aliphatic amino acids like tryptophan and proline may violate the condition
and thus invalidate the asymmetric photolysis scenario, assuming they were
among the primordial amino acids. Alternatively, if CPL photolysis in space is
indeed the source of homochirality of amino acids, then tryptophan and proline
may be crossed out from the list of biogenic amino acids.Comment: To appear in Space Science Reviews, 11 pages, 1 figure (LaTeX
Amino acid metabolism conflicts with protein diversity
The twenty protein coding amino acids are found in proteomes with different
relative abundances. The most abundant amino acid, leucine, is nearly an order
of magnitude more prevalent than the least abundant amino acid, cysteine. Amino
acid metabolic costs differ similarly, constraining their incorporation into
proteins. On the other hand, sequence diversity is necessary for protein
folding, function and evolution. Here we present a simple model for a
cost-diversity trade-off postulating that natural proteomes minimize amino acid
metabolic flux while maximizing sequence entropy. The model explains the
relative abundances of amino acids across a diverse set of proteomes. We found
that the data is remarkably well explained when the cost function accounts for
amino acid chemical decay. More than one hundred proteomes reach comparable
solutions to the trade-off by different combinations of cost and diversity.
Quantifying the interplay between proteome size and entropy shows that
proteomes can get optimally large and diverse
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