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1.
Pascal Verdié Gilles Subra Pierre Chevallet Muriel Amblard Jean Martinez 《International journal of peptide research and therapeutics》2007,13(1-2):337-343
As part of our efforts to design constrained peptide mimics and introduce them in peptide sequences, we set up the synthesis
of racemic N-Fmoc protected hydroxypyrrolidine by reduction of the corresponding oxopyrroline. Hydroxypyrrolidines are synthesized
using amino acid building block and β-ketoester via a 4-steps solid supported route on Wang resin beads. The hydroxypyrrolidine template can be seen as a constrained mimic of
statine. As proof of concept, the pseudopeptide JMV 2776, incorporating this new statine mimic has been synthesized. We replaced
the phenyl statine building block in the sequence of known BACE 1/2 inhibitors by 5-benzyl 2-methyl 4-hydroxypyrrolidine,
using conventional Fmoc SPPS on Rink amide PS resin.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
2.
A problem with studying evolutionary dynamics of mitochondrial (mt) DNA is that classical population genetic techniques cannot
identify selected substitutions because of genetic hitchhiking. We circumvented this problem by employing a candidate complex
approach to study sequence variation in cytochrome c oxidase (COX) genes within and among three distinct Drosophila simulans mtDNA haplogroups. First, we determined sequence variation in complete coding regions for all COX mtDNA and nuclear loci
and their isoforms. Second, we constructed a quaternary structure model of D. simulans COX. Third, we predicted that six of nine amino acid changes in D. simulans mtDNA are likely to be functionally important. Of these seven, genetic crosses can experimentally determine the functional
significance of three. Fourth, we identified two single amino acid changes and a deletion of two consecutive amino acids in
nuclear encoded COX loci that are likely to influence cytochrome c oxidase activity. These data show that linking population genetics and quaternary structure modeling can lead to functional
predictions of specific mtDNA amino acid mutations and validate the candidate complex approach.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
3.
Bartosz Trzaskowski Ludwik Adamowicz Pierre A. Deymier 《Journal of biological inorganic chemistry》2008,13(1):133-137
Density functional theory calculations have been employed to study the interaction between the Zn2+ ion and some standard amino acid models. The highest affinities towards the Zn2+ ion are predicted for serine, cysteine, and histidine. Relatively high affinities are reported also for proline and glutamate/aspartate
residues. It was found that the zinc complexes with cysteine adopt a tetrahedral conformation. Conversely, complexes with
one or two histidine moieties remain in an octahedral geometry, while those with three or more histidine groups adopt a square-planar
geometry.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
4.
5.
The “cognate bias hypothesis” states that early in evolutionary history the biosynthetic enzymes for amino acid x gradually lost residues of x, thereby reducing the threshold for deleterious effects of x scarcity. The resulting reduction in cognate amino acid composition of the enzymes comprising a particular amino acid biosynthetic
pathway is predicted to confer a selective growth advantage on cells. Bioinformatic evidence from protein-sequence data of
two bacterial species previously demonstrated reduced cognate bias in amino acid biosynthetic pathways. Here we show that
cognate bias in amino acid biosynthesis is present in the other domains of life—Archaebacteria and Eukaryota. We also observe
evolutionarily conserved underrepresentations (e.g., glycine in methionine biosynthesis) and overrepresentations (e.g., tryptophan
in asparagine biosynthesis) of amino acids in noncognate biosynthetic pathways, which can be explained by secondary amino
acid metabolism. Additionally, we experimentally validate the cognate bias hypothesis using the yeast Saccharomyces cerevisiae. Specifically, we show that the degree to which growth declines following amino acid deprivation is negatively correlated
with the degree to which an amino acid is underrepresented in the enzymes that comprise its cognate biosynthetic pathway.
Moreover, we demonstrate that cognate fold representation is more predictive of growth advantage than a host of other potential
growth-limiting factors, including an amino acid’s metabolic cost or its intracellular concentration and compartmental distribution.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.
Reviewing
Editor: Dr. Niles Lehman
Ethan O. Perlstein and Benjamin L. de Bivort contributed equally to this work. 相似文献
6.
Structure-dependent relationships between growth temperature of prokaryotes and the amino acid frequency in their proteins 总被引:3,自引:2,他引:1
Saelensminde G Halskau Ø Helland R Willassen NP Jonassen I 《Extremophiles : life under extreme conditions》2007,11(4):585-596
We studied the amino acid frequency and substitution patterns between homologues of prokaryotic species adapted to temperatures
in the range 0–102°C, and found a significant temperature-dependent difference in frequency for many of the amino acids. This
was particularly clear when we analysed the surface and core residues separately. The difference between the surface and the
core is getting more pronounced in proteins adapted to warmer environments, with a more hydrophobic core, and more charged
and long-chained amino acids on the surface of the proteins. We also see that mesophiles have a more similar amino acid composition
to psychrophiles than to thermophiles, and that archea appears to have a slightly different pattern of substitutions than
bacteria.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
7.
Ochiai T Asaoka T Kato T Osaka S Dewa T Yamashita K Gardiner AT Hashimoto H Nango M 《Photosynthesis research》2008,95(2-3):353-361
Synthetic single α-helix hydrophobic polypeptides, which have similar amino acid sequences to the hydrophobic core in the
native light-harvesting 1-β polypeptide from Rhodobacter sphaeroides, formed Zn porphyrin complexes on a gold electrode, as well as in n-octyl-β-glucoside micelles: this process is dependent on the structure of the pigments and the polypeptides. Interestingly,
an enhanced photoelectric current was observed when Zn mesoporphyrin monomer complexed with the synthetic light-harvesting
model polypeptide in an α-helical configuration was assembled with a defined orientation onto the electrode. Analog of these
light-harvesting model complexes are also useful in providing insights into the effect of polypeptide structure on the formation
of light-harvesting complexes on and off electrodes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
8.
Nonnative heme coordination structures emerging upon guanidine hydrochloric acid (GdnHCl) induced unfolding of Hydrogenobacter thermophilus ferricytochrome c
552 were characterized by means of paramagnetic NMR. The heme coordination structure possessing the N-terminal amino group of
the peptide chain in place of axial Met (His–Nterm form) was determined in the presence of GdnHCl concentrations in excess of 1.5 M at neutral pH. The stability of the His–Nterm form at pH 7.0 was found to be comparable with that of the bis-His form which has been recognized as a major nonnative heme
coordination structure in cytochrome c folding/unfolding. Consequently, in addition to the bis-His form, the His–Nterm form is a substantial intermediate which affects the pathway and kinetics of the folding/unfolding of cytochromes c, of which the N-terminal amino groups are not acetylated.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
9.
Allison N. Tegge Bruce R. Southey Jonathan V. Sweedler Sandra L. Rodriguez-Zas 《Mammalian genome》2008,19(2):106-120
Neuropeptides are an important class of signaling molecules that result from complex and variable posttranslational processing
of precursor proteins and thus are difficult to identify based solely on genomic information. Bioinformatics prediction of
precursor cleavage sites can support effective biochemical characterization of neuropeptides. Neuropeptide cleavage models
were developed using comprehensive human, mouse, rat, and cattle precursor data sets and used to compare predicted neuropeptide
processing across these species. Logistic regression and artificial neural network models were used to predict cleavages based
on amino acid and physiochemical properties of amino acids at precursor sequence locations proximal to cleavage. Correct cleavage
classification rates across species and models ranged from 85% to 100%, suggesting that amino acid and amino acid properties
have major impact on the probability of cleavage and that these factors have comparable effects in human, mouse, rat, and
cattle. The variable accuracy of each species-specific model to predict cleavage sites indicated that there are species- and
precursor-specific processing patterns. Prediction of mouse cleavages using rat models was highly accurate, yet the reverse
was not observed. Sensitivity and specificity revealed that logistic models are well suited to maximize the rate of true noncleavage
predictions with moderate rates of true cleavage predictions; meanwhile, artificial neural networks maximize the rate of true
cleavage predictions with moderate to low true noncleavage predictions. Logistic models also provided insights into the strength
of the amino acid associations with cleavage. Prediction of neuropeptide cleavage sites using human, mouse, rat, and cattle
models are available at .
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Allison Tegge and Bruce Southey contributed equally to this work. 相似文献
10.
DNA shuffling was carried out with two chitosanase genes belonging to glycoside hydrolase family eight from Bacillus cereus KNUC51 and B. cereus KNUC55. The shuffled products, YM18 and YM20, which showed higher activity than the parents at 40°C, were selected for further
studies. The 50 kDa chitosanases were purified using affinity chromatography with glutathione-Sepharose 4B. In general, the
specific activity of YM18 is enhanced 250% and that of YM20 is 350% compared to the parents. YM20 exhibits a shift of the
optimal pH level from 5.5 to 6.5. DNA sequence analysis revealed that YM18 and YM20 contained 2 amino acid substitutions (I13T
and A87V for YM18; K66R and N352S for YM20). We presumed that these amino acid substitutions increase the specific activity
and change the property of the two variants.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
11.
High amino acid coverage labeling of the mammalian G protein coupled receptors (GPCR) rhodopsin was established with 15N and 15N/13C isotopes. Rhodopsin was expressed at preparative scale in HEK293S cells and studied in full-length by NMR spectroscopy in
detergent micelle solution. This resulted in the assignment and detailed study of the dynamic properties of the C-terminus
of rhodopsin. The rhodopsin C-terminus is immobilized until Ala333, after which it becomes unstructured.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
12.
Saša N. Malkov Miodrag V. Živković Miloš V. Beljanski Srđan Đ. Stojanović Snežana D. Zarić 《The protein journal》2009,28(2):74-86
Using the data from Protein Data Bank the correlations of primary and secondary structures of proteins were analyzed. The
correlation values of the amino acids and the eight secondary structure types were calculated, where the position of the amino
acid and the position in sequence with the particular secondary structure differ at most 25. The diagrams describing these
results indicate that correlations are significant at distances between −9 and 10. The results show that the substituents
on Cβ or Cγ atoms of amino acid play major role in their preference for particular secondary structure at the same position
in the sequence, while the polarity of amino acid has significant influence on α-helices and strands at some distance in the
sequence. The diagrams corresponding to polar amino acids are noticeably asymmetric. The diagrams point out the exchangeability
of residues in the proteins; the amino acids with similar diagrams have similar local folding requirements.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
13.
In this work we perform a comparative study on the location of positively selected sites (those likely responsible for defining
specificity differences) at the S-RNase gene, the pistil component of the gametophytic self-incompatibility system. For Plantaginaceae and Rosaceae (Prunus and Pyrus/Malus) this is the first study of this kind. A clear sign of positive selection was observed for 13, 17, and 27 amino acid sites
in Solanaceae, Prunus, and Pyrus/Malus, respectively, using two different methodologies. In Plantaginaceae no clear positively selected sites were identified. Possible
reasons for this result are discussed. Indirect experimental evidence suggests that the identified positively selected amino
acid sites play a role in specificity determination. The percentage of positively selected sites is similar in Solanaceae
and Rosaceae but the location of those sites is different.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.
Reviewing Editor: Dr. Martin Kreitman 相似文献
14.
Ant-dispersed plants usually produce seeds with appendages (elaiosomes) as reward for ants. Plants that produce high-quality
elaiosomes benefit because ants preferentially disperse their diaspores. We therefore hypothesized that seeds and elaiosomes
differ in chemical composition in ways that make elaiosomes of high nutritional quality for ants, capable of providing essential
dietary components that explain the increased fitness and higher gyne production documented for colonies with elaiosome consumption.
To test the hypothesis we analysed the content and composition of lipids, amino acids, soluble carbohydrates, proteins and
starch in seeds and elaiosomes of 15 central European ant-dispersed plants. After separating the different fractions, total
lipids were determined gravimetrically, fatty acids and soluble carbohydrates were detected by gas chromatography (GC) and
GC–mass spectrometry, free amino acids by an amino acid analyser while starch and protein were analysed photometrically. Seeds
accumulated high molecular weight compounds such as proteins and starch, whereas elaiosomes accumulated more easily digestible
low molecular weight compounds such as amino acids and monosaccharides. Analysis of similarities and similarity percentages
analysis demonstrated that the composition of fatty acids, free amino acids and carbohydrates differed markedly between elaiosomes
and seeds. The most important difference was in total amino acid content, which was on average 7.5 times higher in elaiosomes
than in seeds. The difference was especially marked for the nitrogen-rich amino acid histidine. The availability of essential
nutrients and, in some species, the higher nitrogen content in elaiosomes suggest that their nutritional value for larvae
plays a key role in this interaction.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
15.
Explicit evaluation of the accuracy and power of maximum likelihood and Bayesian methods for detecting site-specific positive
Darwinian selection presents a challenge because selective consequences of single amino acid changes are generally unknown.
We exploited extensive molecular and functional characterization of amino acid substitutions in the plant gene eIF4E to evaluate the performance of these methods in detecting site-specific positive selection. We documented for the first time
a molecular signature of positive selection within a recessive resistance gene in plants. We then used two statistical platforms,
Phylogenetic Analysis Using Maximum Likelihood and Hypothesis Testing Using Phylogenies (HyPhy), to look for site-specific
positive selection. Their relative power and accuracy are assessed by comparing the sites they identify as being positively
selected with those of resistance-determining amino acids. Our results indicate that although both methods are surprisingly
accurate in their identification of resistance sites, HyPhy appears to more accurately identify biologically significant amino
acids using our data set.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
J. R. Cavatorta and A. E. Savage have contributed equally to this work. 相似文献
16.
Maximum-likelihood models of codon and amino acid substitution were used to analyze the lung-specific surfactant protein C
(SP-C) from terrestrial, semi-aquatic, and diving mammals to identify lineages and amino acid sites under positive selection.
Site models used the nonsynonymous/synonymous rate ratio (ω) as an indicator of selection pressure. Mechanistic models used
physicochemical distances between amino acid substitutions to specify nonsynonymous substitution rates. Site models strongly
identified positive selection at different sites in the polar N-terminal extramembrane domain of SP-C in the three diving
lineages: site 2 in the cetaceans (whales and dolphins), sites 7, 9, and 10 in the pinnipeds (seals and sea lions), and sites
2, 9, and 10 in the sirenians (dugongs and manatees). The only semi-aquatic contrast to indicate positive selection at site
10 was that including the polar bear, which had the largest body mass of the semi-aquatic species. Analysis of the biophysical
properties that were influential in determining the amino acid substitutions showed that isoelectric point, chemical composition
of the side chain, polarity, and hydrophobicity were the crucial determinants. Amino acid substitutions at these sites may
lead to stronger binding of the N-terminal domain to the surfactant phospholipid film and to increased adsorption of the protein
to the air-liquid interface. Both properties are advantageous for the repeated collapse and reinflation of the lung upon diving
and resurfacing and may reflect adaptations to the high hydrostatic pressures experienced during diving.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Reviewing Editor: Dr. Richard Kliman 相似文献
17.
Schlösser T Wiesenburg A Gätgens C Funke A Viets U Vijayalakshmi S Nieland S Stahmann KP 《Applied microbiology and biotechnology》2007,76(3):569-578
We performed directed evolution on a chemically synthesized 1,533-bp recombinant beta-galactosidase gene from Pyrococcus woesei. More than 200,000 variant colonies in each round of directed evolution were screened using the pYPX251 vector and host strain
Rosetta-Blue (DE3). One shifted beta-galactosidase to beta-glucuronidase mutant, named YG6762, was obtained after four rounds
of directed evolution and screening. This mutant had eight mutated amino acid residues. T29A, V213I, L217M, N277H, I387V,
R491C, and N496D were key mutations for high beta-glucuronidase activity, while E414D was not essential because the mutation
did not lead to a change in beta-glucuronidase activity. The amino acid site 277 was the most essential because mutating H
back to N resulted in a 50% decrease in beta-glucuronidase activity at 37°C. We also demonstrated that amino acid 277 was
the most essential site, as the mutation from N to H resulted in a 1.5-fold increase in beta-glucuronidase activity at 37°C.
Although most single amino acid changes lead to less than a 20% increase in beta-glucuronidase activity, the YG6762 variant,
which was mutated at all eight amino acid sites, had a beta-glucuronidase activity that was about five and seven times greater
than the wild-type enzyme at 37 and 25°C, respectively.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
18.
The issue of amino acid depth in proteins gives important insights to our understanding of protein’s three-dimensional structure.
There has already been much research done in mathematical and statistical sciences regarding the general definitions, properties
and algorithms describing the particle depth of spatially extended systems. We constructed a method of calculating the amino
acids depths and applied it to a set of 527 protein structures. We propose the introduction of amino acid depth tendency factors
for three-dimensional structures of proteins. The depth tendency factors relate not only to the hydrophobicity indices but
also to the electrostatic charge. We found a relationship between the protein size and the number of residues using the distance
between the deepest residue and surface residues. We made a prediction regarding the number of residues on the surface of
a protein, the deepest amino acid, and the average depth, all of which are fitted well to a linear functional relationship
with the length of the protein. Finally, we have predicted the depths of multiple peptides in protein’s three-dimension structure.
Electronic supplementary material The online version of this article () contains supplementary material, which is available to authorized users. 相似文献
19.
Discrimination of Lysosomal membrane proteins (LMP’s) from folding types of globular (GPs) and other membrane proteins (OtMPs) is an important task both for identifying LMPs from genomic sequences and for the successful prediction of their secondary and tertiary structures. We have systematically analyzed the amino acid frequencies as well as dipeptide count of GPs, LMPs and OtMPs. Based on the above calculated single amino acid frequency combined with dipeptide count information, we statistically discriminated LMPs from GPs and OtMPs. This approach correctly classified the LMPs with an accuracy of 95 %. On the other hand, the amino acid frequency alone can discriminate LMPs with an accuracy of only 79 %. Similarly dipeptide count alone has an accuracy of 87 % for the discrimination of LMPs. Thus the combined information of both amino acid frequencies and dipeptide composition gives us significant high accurate results.
Electronic supplementary material
The online version of this article (doi:10.1007/s11693-014-9153-7) contains supplementary material, which is available to authorized users. 相似文献20.
Benjamin L. de Bivort Ethan O. Perlstein Sam Kunes Stuart L. Schreiber 《Journal of molecular evolution》2009,68(5):490-497
The metabolic cycle of Saccharomyces cerevisiae consists of alternating oxidative (respiration) and reductive (glycolysis) energy-yielding reactions. The intracellular concentrations
of amino acid precursors generated by these reactions oscillate accordingly, attaining maximal concentration during the middle
of their respective yeast metabolic cycle phases. Typically, the amino acids themselves are most abundant at the end of their
precursor’s phase. We show that this metabolic cycling has likely biased the amino acid composition of proteins across the
S. cerevisiae genome. In particular, we observed that the metabolic source of amino acids is the single most important source of variation
in the amino acid compositions of functionally related proteins and that this signal appears only in (facultative) organisms
using both oxidative and reductive metabolism. Periodically expressed proteins are enriched for amino acids generated in the
preceding phase of the metabolic cycle. Proteins expressed during the oxidative phase contain more glycolysis-derived amino
acids, whereas proteins expressed during the reductive phase contain more respiration-derived amino acids. Rare amino acids
(e.g., tryptophan) are greatly overrepresented or underrepresented, relative to the proteomic average, in periodically expressed
proteins, whereas common amino acids vary by a few percent. Genome-wide, we infer that 20,000 to 60,000 residues have been
modified by this previously unappreciated pressure. This trend is strongest in ancient proteins, suggesting that oscillating
endogenous amino acid availability exerted genome-wide selective pressure on protein sequences across evolutionary time.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Benjamin L. de Bivort and Ethan O. Perlstein have contributed equally to this work. 相似文献