bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological implications of SNPs in signal peptide domains of human proteins
Authors: Jarjanazi Hamdi , Savas Sevtap , Pabalan Noel , Dennis James W. , Ozcelik Hilmi 
Published: August 2007

AbstractProteins destined for secretion or membrane compartments possess signal peptides for insertion into the membrane. The signal peptide is therefore critical for localization and function of cell surface receptors and ligands that mediate cell–cell communication. About 4% of all human proteins listed in UniProt database have signal peptide domains in their N terminals. A comprehensive literature survey was performed to retrieve functional and disease associated genetic variants in the signal peptide domains of human proteins. In 21 human proteins we have identified 26 disease associated mutations within their signal peptide domains, 14 mutations of which have been experimentally shown to impair the signal peptide function and thus influence protein transportation. We took advantage of SignalP 3.0 predictions to characterize the signal peptide prediction score differences between the mutant and the wild‐type alleles of each mutation, as well as 189 previously uncharacterized single nucleotide polymorphisms (SNPs) found to be located in the signal peptide domains of 165 human proteins. Comparisons of signal peptide prediction outcomes of mutations and SNPs, have implicated SNPs potentially impacting the signal peptide function, and thus the cellular localization of the human proteins. The majority of the top candidate proteins represented membrane and secreted proteins that are associated with molecular transport, cell signaling and cell to cell interaction processes of the cell. This is the first study that systematically characterizes genetic variation occurring in the signal peptides of all human proteins. This study represents a useful strategy for prioritization of SNPs occurring within the signal peptide domains of human proteins. Functional evaluation of candidates identified herein may reveal effects on major cellular processes including immune cell function, cell recognition and adhesion, and signal transduction. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Prediction of kinase‐specific phosphorylation sites with sequence features by a log‐odds ratio approach
Authors: Li Tingting , Li Fei , Zhang Xuegong 
Published: August 2007

AbstractProtein phosphorylation plays important roles in a variety of cellular processes. Detecting possible phosphorylation sites and their corresponding protein kinases is crucial for studying the function of many proteins. This article presents a new prediction system, called PhoScan, to predict phosphorylation sites in a kinase‐family‐specific way. Common phosphorylation features and kinase‐specific features are extracted from substrate sequences of different protein kinases based on the analysis of published experiments, and a scoring system is developed for evaluating the possibility that a peptide can be phosphorylated by the protein kinase at the specific site in its sequence context. PhoScan can achieve a specificity of above 90% with sensitivity around 90% at kinase‐family level on the data experimented. The system is applied on a set of human proteins collected from Swiss‐Prot and sets of putative phosphorylation sites are predicted for protein kinase A, cyclin‐dependent kinase, and casein kinase 2 families. PhoScan is available at http://bioinfo.au.tsinghua.edu.cn/phoscan/. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Structure of biosynthetic N‐acetylornithine aminotransferase from Salmonella typhimurium: Studies on substrate specificity and inhibitor binding
Authors: Rajaram V. , Ratna Prasuna P. , Savithri H. S. , Murthy M. R. N. 
Published: August 2007

AbstractAcetylornithine aminotransferase (AcOAT) is one of the key enzymes involved in arginine metabolism and catalyzes the conversion of N‐acetylglutamate semialdehyde to N‐acetylornithine (AcOrn) in the presence of L‐glutamate. It belongs to the Type I subgroup II family of pyridoxal 5′‐phosphate (PLP) dependent enzymes. E. coli biosynthetic AcOAT (eAcOAT) also catalyzes the conversion of N‐succinyl‐L‐2‐amino‐6‐oxopimelate to N‐succinyl‐L,L‐diaminopimelate, one of the steps in lysine biosynthesis. In view of the critical role of AcOAT in lysine and arginine biosynthesis, structural studies were initiated on the enzyme from S. typhimurium (sAcOAT). The Km and kcat/Km values determined with the purified sAcOAT suggested that the enzyme had much higher affinity for AcOrn than for ornithine (Orn) and was more efficient than eAcOAT. sAcOAT was inhibited by gabaculine (Gcn) with an inhibition constant (Ki) of 7 μM and a second‐order rate constant (k2) of 0.16 mM−1 s−1. sAcOAT, crystallized in the unliganded form and in the presence of Gcn or L‐glutamate, diffracted to a maximum resolution of 1.90 Å and contained a dimer in the asymmetric unit. The structure of unliganded sAcOAT showed significant electron density for PLP in only one of the subunits (subunit A). The asymmetry in PLP binding could be attributed to the ordering of the loop Lαk‐βm in only one subunit (subunit B; the loop from subunit B comes close to the phosphate group of PLP in subunit A). Structural and spectral studies of sAcOAT with Gcn suggested that the enzyme might have a low affinity for PLP‐Gcn complex. Comparison of sAcOAT with T. thermophilus AcOAT and human ornithine aminotransferase suggested that the higher specificity of sAcOAT towards AcOrn may not be due to specific changes in the active site residues but could result from minor conformational changes in some of them. This is the first structural report of AcOAT from a mesophilic organism and could serve as a basis for drug design as the enzyme is important for bacterial cell wall biosynthesis. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Coupling of the guanosine glycosidic bond conformation and the ribonucleotide cleavage reaction: Implications for barnase catalysis
Authors: Roca Maite , De Maria Leonardo , Wodak Shoshana J. , Moliner Vicente , Tuñón Iñaki , Giraldo Jesús 
Published: August 2007

AbstractTo examine the possible relationship of guanine‐dependent GpA conformations with ribonucleotide cleavage, two potential of mean force (PMF) calculations were performed in aqueous solution. In the first calculation, the guanosine glycosidic (Gχ) angle was used as the reaction coordinate, and computations were performed on two GpA ionic species: protonated (neutral) or deprotonated (negatively charged) guanosine ribose O2 ′. Similar energetic profiles featuring two minima corresponding to the anti and syn Gχ regions were obtained for both ionic forms. For both forms the anti conformation was more stable than the syn, and barriers of ∼4 kcal/mol were obtained for the anti → syn transition. Structural analysis showed a remarkable sensitivity of the phosphate moiety to the conformation of the Gχ angle, suggesting a possible connection between this conformation and the mechanism of ribonucleotide cleavage. This hypothesis was confirmed by the second PMF calculations, for which the O2 ′P distance for the deprotonated GpA was used as reaction coordinate. The computations were performed from two selected starting points: the anti and syn minima determined in the first PMF study of the deprotonated guanosine ribose O2′. The simulations revealed that the O2 ′ attack along the syn Gχ was more favorable than that along the anti Gχ: energetically, significantly lower barriers were obtained in the syn than in the anti conformation for the OP bond formation; structurally, a lesser O2 ′P initial distance, and a better suited orientation for an in‐line attack was observed in the syn relative to the anti conformation. These results are consistent with the catalytically competent conformation of barnase–ribonucleotide complex, which requires a guanine syn conformation of the substrate to enable abstraction of the ribose H2 ′ proton by the general base Glu73, thereby suggesting a coupling between the reactive substrate conformation and enzyme structure and mechanism. Proteins 2008. © 2007 Wiley‐Liss, Inc.
A model study of protein nascent chain and cotranslational folding using hydrophobic‐polar residues
Authors: Lu Hsiao‐Mei , Liang Jie 
Published: August 2007

AbstractTo study protein nascent chain folding during biosynthesis, we investigate the folding behavior of models of hydrophobic and polar (HP) chains at growing length using both two‐dimensional square lattice model and an optimized three‐dimensional 4‐state discrete off‐lattice model. After enumerating all possible sequences and conformations of HP heteropolymers up to length N = 18 and N = 15 in two and three‐dimensional space, respectively, we examine changes in adopted structure, stability, and tolerance to single point mutation as the nascent chain grows. In both models, we find that stable model proteins have fewer folded nascent chains during growth, and often will only fold after reaching full length. For the few occasions where partial chains of stable proteins fold, these partial conformations on average are very similar to the corresponding parts of the final conformations at full length. Conversely, we find that sequences with fewer stable nascent chains and sequences with native‐like folded nascent chains are more stable. In addition, these stable sequences in general can have many more point mutations and still fold into the same conformation as the wild type sequence. Our results suggest that stable proteins are less likely to be trapped in metastable conformations during biosynthesis, and are more resistant to point‐mutations. Our results also imply that less stable proteins will require the assistance of chaperone and other factors during nascent chain folding. Taken together with other reported studies, it seems that cotranslational folding may not be a general mechanism of in vivo protein folding for small proteins, and in vitro folding studies are still relevant for understanding how proteins fold biologically. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Kinetically driven refolding of the hyperstable EBNA1 origin DNA‐binding dimeric β‐barrel domain into amyloid‐like spherical oligomers
Authors: Freire Eleonora , Oddo Cristian , Frappier Lori , de Prat‐Gay Gonzalo 
Published: August 2007

AbstractThe Epstein‐Barr nuclear antigen 1 (EBNA1) is essential for DNA replication and episome segregation of the viral genome, and participates in other gene regulatory processes of the Epstein‐Barr virus in benign and malignant diseases related to this virus. Despite the participation of other regions of the protein in evading immune response, its DNA binding, dimeric β‐barrel domain (residues 452–641) is necessary and sufficient for the main functions. This domain has an unusual topology only shared by another viral origin binding protein (OBP), the E2 DNA binding domain of papillomaviruses. Both the amino acid and DNA target sequences are completely different for these two proteins, indicating a link between fold conservation and function. In this work we investigated the folding and stability of the DNA binding domain of EBNA1 OBP and found it is extremely resistant to chemical, temperature, and pH denaturation. The thiocyanate salt of guanidine is required for obtaining a complete transition to a monomeric unfolded state. The unfolding reaction is extremely slow and shows a marked uncoupling between tertiary and secondary structure, indicating the presence of intermediate species. The Gdm.SCN unfolded protein refolds to fully soluble and spherical oligomeric species of 1.2 MDa molecular weight, with identical fluorescence centre of spectral mass but different intensity and different secondary structure. The refolded spherical oligomers are substantially less stable than the native recombinant dimer. In keeping with the substantial structural rearrangement in the oligomers, the spherical oligomers do not bind DNA, indicating that the DNA binding site is either disrupted or participates in the oligomerization interface. The puzzling extreme stability of a dimeric DNA binding domain from a protein from a human infecting virus in addition to a remarkable kinetically driven folding where all molecules do not return to the most stable original species suggests a co‐translational and directional folding of EBNA1in vivo, possibly assisted by folding accessory proteins. Finally, the oligomers bind Congo red and thioflavin‐T, both characteristic of repetitive β‐sheet elements of structure found in amyloids and their soluble precursors. The stable nature of the “kinetically trapped” oligomers suggest their value as models for understanding amyloid intermediates, their toxic nature, and the progress to amyloid fibers in misfolding diseases. The possible role of the EBNA1 spherical oligomers in the virus biology is discussed. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Modelling suppressed and active convection. Comparing a numerical weather prediction, cloud‐resolving and single‐column model
Authors: Petch J. C. , Willett M. , Wong R. Y. , Woolnough S. J. 
Published: August 2007

AbstractThis paper describes the design of and basic results from a case study to compare simulations of convection over the Tropical West Pacific. Simulations are carried out using a cloud‐resolving model (CRM), a global numerical weather prediction (NWP) model and a single‐column version of the NWP model (SCM). The experimental design for each model type is discussed and then results are compared. The periods simulated each include a regime with strong convective activity, a much more suppressed regime with far less convection, as well as the transition between these regimes. The description of the design and basic results from this study are given in some detail, as a study including all these model types is relatively new. Comparing the local forcing due to the dynamics in the NWP model with the observed forcing used to drive the CRM and SCM it is found that there is good agreement for one period chosen but significant differences for another. This is also seen in fields such as rain rate and top‐of‐atmosphere radiation. Using the period with good agreement we are able to identify examples of biases in the NWP model that are also reproduced in the SCM. Also discussed are examples of biases in the NWP simulation that are not reproduced in the SCM. It is suggested that understanding which biases in the SCM are consistent with the full NWP model can help focus the use of an SCM in this framework. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd
The idempotent Dirac density matrix as a functional of the diagonal ground‐state electron density obtained from diffraction experiments
Authors: March N. H. 
Published: August 2007

AbstractThe idempotent Dirac single‐particle (s) density matrix γs(r,r′) as a functional of a given one‐body potential V(r) was constructed to all orders in perturbation theory by March and Murray, some four and a half decades ago. While the subsequent theorems of DFT ensure that V is a functional of the ground‐state density ρ, only recently has V been written explicitly as a functional of the Dirac density matrix γs. In the present study, both functionals γs[ρ] and γs[V] are studied; first for some model potentials V and somewhat then more generally in terms of partial differential equations. This later procedure should open up a route to treat numerically molecules of biophysical interest, provided the ground‐state electron density ρ(r) is initially determined from diffraction experiments. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Theoretical study of ignition reactions of linear symmetrical monoethers as potential diesel fuel additives: DFT calculations
Authors: Marrouni Karim El , Abou‐Rachid Hakima , Kaliaguine Serge 
Published: August 2007

AbstractThis work investigates the chemical reactivity of four linear symmetrical monoethers with molecular oxygen. Such oxygenated compounds may be considered as potential diesel fuel additives in order to reduce the ignition delay in diesel fuel engines. For this purpose, a kinetic study is proposed to clarify the relation between the molecular structure of the fuel molecule and its ignition properties. To this end, DFT calculations were performed for these reactions using B3LYP/6‐311G(d,p) and BH&HLYP/6‐311G(d,p) to determine structures, energies, and vibrational frequencies of stationary points as well as activated complexes involved in each gas‐phase combustion initiation reaction of the monoethers CH3OCH3, C2H5OC2H5, C3H7OC3H7, or C4H9OC4H9 with molecular oxygen. This theoretical kinetic study was carried out using electronic structure results and the transition state theory, to assess the rate constants for all studied combustion reactions. As it has been shown in our previous work [Abou‐Rachid et al., J Mol Struct (Theochem) 2003, 621, 293], the cetane number (CN) of a pure organic molecule depends on the initiation rate of its homogeneous gas‐phase reaction with molecular oxygen. Indeed, the calculated initiation rate constants of the H‐abstraction process of linear monoethers with O2 show a very good correlation with experimental CN data of these pure compounds at T = 1,000 K. This temperature is representative of the operating conditions of a diesel fuel engine. © 2007 Wiley Periodicals, Inc. Int Quantum Chem, 2008
Possible properties of positron states in physics and chemistry of a surface and in semiconductor nanotechnologies
Authors: Grafutin V. I. , Svetlov‐Prokop'Ev E. P. , Timoshenkov S. P. , Kalugin V. V. , Artemov E. I. 
Published: August 2007

AbstractThe possibilities of positron beam annihilation spectroscopy for research quantum dots, quantum wells, quantum wires in chemistry and physics of surface and semiconductor nanotechnologies are discussed. The relations between the basic characteristics of positron annihilation this states and parameters of these structures were obtained.
High‐order harmonic generation of heteronuclear diatomic molecules in intense ultrashort laser fields: An all‐electron TDDFT study
Authors: Heslar John , Carrera Juan , Telnov Dmitry , Chu Shih‐I 
Published: August 2007

AbstractWe present a time‐dependent density functional theory (TDDFT), with proper asymptotic long‐range potential, for nonperturbative treatment of multiphoton processes of homonuclear and heteronuclear diatomic molecules in intense ultrashort laser fields. A time‐dependent two‐center generalized pseudospectral method is presented for accurate and efficient treatment of the TDDFT equations in space and time. The procedure allows nonuniform and optimal spatial grid discretization of the Hamiltonian in prolate spheroidal coordinates and a split‐operator scheme in the energy representation is used for the time propagation of the individual molecular spin‐orbital. The theory is applied to a detailed all‐electron study of multiphoton ionization (MPI) and high‐order harmonic generation (HHG) processes of N2 and CO molecules in intense laser pulses. The results reveal intriguing and substantially different nonlinear optical response behaviors for N2 and CO, despite the fact that CO has only a very small permanent dipole moment. In particular, we found that the MPI rate for CO is higher than that of N2. Furthermore, while laser excitation of the homonuclear N2 molecule can generate only odd harmonics, both even and odd harmonics can be produced from the heteronuclear CO molecule. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Screening method for the addition of bovine blood‐based binding agents to food using liquid chromatography triple quadrupole mass spectrometry
Authors: Grundy Helen H. , Reece Paul , Sykes Mark D. , Clough Julie A. , Audsley Neil , Stones Robert 
Published: August 2007

AbstractWe report the development of a qualitative method to detect the addition of blood‐based binding agents to food products. The method is based on the detection of species‐specific marker peptides, fibrinopeptides, released from the blood protein fibrinogen during gelling of the blood protein by thrombin. The fibrinopeptides were isolated from foods spiked with commercial bovine binding agent by acid precipitation followed by enrichment using solid‐phase extraction and analysed by liquid chromatography electrospray ionisation triple quadrupole mass spectrometry. Fibrinopeptide A was found to be an effective marker in fresh, processed and cooked food matrices spiked with 5% (v/w) bovine binding agent. © Crown copyright 2007. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Quantitative determination of acetylcholine in microdialysis samples using liquid chromatography/atmospheric pressure spray ionization mass spectrometry
Authors: Keski‐Rahkonen Pekka , Lehtonen Marko , Ihalainen Jouni , Sarajärvi Timo , Auriola Seppo 
Published: August 2007

AbstractA fast, simple and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the determination of acetylcholine in rat brain microdialysis samples. The chromatographic separation was achieved in 3 min on a reversed‐phase column with isocratic conditions using a mobile phase containing 2% (v/v) of acetonitrile and 0.05% (v/v) of trifluoroacetic acid (TFA). A stable isotope‐labeled internal standard was included in the analysis and detection was carried out with a linear ion trap mass spectrometer using selected reaction monitoring (SRM). Analyte ionization was performed with an atmospheric pressure chemical ionization (APCI) source without applying discharge current (atmospheric pressure spray ionization). This special ionization technique offered significant advantages over electrospray ionization for the analysis of acetylcholine with reversed‐phase ion‐pairing chromatography. The lower limit of quantification was 0.15 nM (1.5 fmol on‐column) and linearity was maintained over the range of 0.15–73 nM, providing a concentration range that is significantly wider than that of the existing LC/MS methods. Good accuracy and precision were obtained for concentrations within the standard curve range. The method was validated and has been used extensively for the determination of acetylcholine in rat brain microdialysis samples. Copyright © 2007 John Wiley & Sons, Ltd.
Simultaneous determination of atracurium and its metabolite laudanosine in post‐mortem fluids by liquid chromatography/multiple‐stage mass spectrometry on an ion trap
Authors: Ferrara Santo Davide , Nalesso Alessandro , Castagna Franca , Montisci Massimo , Vogliardi Susanna , Favretto Donata 
Published: August 2007

AbstractA method was developed to accurately quantify atracurium (a non‐depolarizing skeletal muscle relaxant) and its metabolite laudanosine in post‐mortem specimens. Analytes were isolated from blood and tissues by liquid/liquid extraction after adding vecuronium as an internal standard. Chromatographic separation was accomplished by gradient elution in a Synergy Max RP 150 × 2.1 mm column. Positive ion electrospray ionization and mass spectrometric analyses were carried out in an ion trap mass spectrometer under collision‐induced dissociation conditions. The method proved selective and sensitive, and was validated in post‐mortem blood, heart, lung and liver in the range of 1–2000 ng/mL (blood) and 5–5000 ng/g (tissues); the limits of quantification obtained were 1 ng/mL in blood and 5 ng/g in tissues. Copyright © 2007 John Wiley & Sons, Ltd.