bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonequilibrium Plasma‐Activated Antimicrobial Solutions are Broad‐Spectrum and Retain their Efficacies for Extended Period of Time
Authors: Ercan Utku K. , Wang Hong , Ji Haifeng , Fridman Gregory , Brooks Ari D. , Joshi Suresh G. 
Published: April 2013

AbstractBy applying dielectric‐barrier discharge nonthermal plasma technique, we have treated fluids and generated antimicrobial solutions, tested for properties such as changes in pH, temperature, delay time, holding time, fluid‐aging, and detection and comparison of acid and hydrogen peroxide. All plasma‐treated solutions showed strong biocidal activity, and among them, NAC solution was the most powerful, inactivated biofilms of tested microorganisms in 15 min of holding time. During accelerated aging experiments, plasma‐treated NAC solution exhibited the equivalent of two years of shelf. These results indicate that it retained its antimicrobial properties for an extended period against a wide range of multidrug‐resistant pathogens, making it an excellent candidate for further testing in vivo.magnified image
A multi‐faceted analysis of RutD reveals a novel family of α/β hydrolases
Authors: Knapik Aleksandra A. , Petkowski Janusz J. , Otwinowski Zbyszek , Cymborowski Marcin T. , Cooper David R. , Majorek Karolina A. , Chruszcz Maksymilian , Krajewska Wanda M. , Minor Wladek 
Published: April 2013

AbstractThe rut pathway of pyrimidine catabolism is a novel pathway that allows pyrimidine bases to serve as the sole nitrogen source in suboptimal temperatures. The rut operon in E. coli evaded detection until 2006, yet consists of seven proteins named RutA, RutB, etc. through RutG. The operon is comprised of a pyrimidine transporter and six enzymes that cleave and further process the uracil ring. Herein, we report the structure of RutD, a member of the α/β hydrolase superfamily, which is proposed to enhance the rate of hydrolysis of aminoacrylate, a toxic side product of uracil degradation, to malonic semialdehyde. Although this reaction will occur spontaneously in water, the toxicity of aminoacrylate necessitates catalysis by RutD for efficient growth with uracil as a nitrogen source. RutD has a novel and conserved arrangement of residues corresponding to the α/β hydrolase active site, where the nucleophile's spatial position occupied by Ser, Cys, or Asp of the canonical catalytic triad is replaced by histidine. We have used a combination of crystallographic structure determination, modeling and bioinformatics, to propose a novel mechanism for this enzyme. This approach also revealed that RutD represents a previously undescribed family within the α/β hydrolases. We compare and contrast RutD with PcaD, which is the closest structural homolog to RutD. PcaD is a 3‐oxoadipate‐enol‐lactonase with a classic arrangement of residues in the active site. We have modeled a substrate in the PcaD active site and proposed a reaction mechanism. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Structural insights into catalysis by βC‐S lyase from Streptococcus anginosus
Authors: Kezuka Yuichiro , Yoshida Yasuo , Nonaka Takamasa 
Published: April 2013

AbstractHydrogen sulfide (H2S) is a causative agent of oral malodor and may play an important role in the pathogenicity of oral bacteria such as Streptococcus anginosus. In this microorganism, H2S production is associated with βC‐S lyase (Lcd) encoded by lcd gene, which is a pyridoxal 5′‐phosphate (PLP)‐dependent enzyme that catalyzes the α,β‐elimination of sulfur‐containing amino acids. When Lcd acts on L‐cysteine, H2S is produced along with pyruvate and ammonia. To understand the H2S‐producing mechanism of Lcd in detail, we determined the crystal structures of substrate‐free Lcd (internal aldimine form) and two reaction intermediate complexes (external aldimine and α‐aminoacrylate forms). The formation of intermediates induced little changes in the overall structure of the enzyme and in the active site residues, with the exception of Lys234, a PLP‐binding residue. Structural and mutational analyses highlighted the importance of the active site residues Tyr60, Tyr119, and Arg365. In particular, Tyr119 forms a hydrogen bond with the side chain oxygen atom of L‐serine, a substrate analog, in the external aldimine form suggesting its role in the recognition of the sulfur atom of the true substrate (L‐cysteine). Tyr119 also plays a role in fixing the PLP cofactor at the proper position during catalysis through binding with its side chain. Finally, we partly modified the catalytic mechanism known for cystalysin, a βC‐S lyase from Treponema denticola, and proposed an improved mechanism, which seems to be common to the βC‐S lyases from oral bacteria. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Motion of transfer RNA from the A/T state into the A‐site using docking and simulations
Authors: Caulfield Thomas , Devkota Batsal 
Published: April 2013

AbstractThe ribosome catalyzes peptidyl transfer reactions at the growing nascent polypeptide chain. Here, we present a structural mechanism for selecting cognate over near‐cognate A/T transfer RNA (tRNA). In part, the structural basis for the fidelity of translation relies on accommodation to filter cognate from near‐cognate tRNAs. To examine the assembly of tRNAs within the ribonucleic–riboprotein complex, we conducted a series of all‐atom molecular dynamics (MD) simulations of the entire solvated 70S Escherichia coli ribosome, along with its associated cofactors, proteins, and messenger RNA (mRNA). We measured the motion of the A/T state of tRNA between initial binding and full accommodation. The mechanism of rejection was investigated. Using novel in‐house algorithms, we determined trajectory pathways. Despite the large intersubunit cavity, the available space is limited by the presence of the tRNA, which is equally large. This article describes a “structural gate,” formed between helices 71 and 92 on the ribosomal large subunit, which restricts tRNA motion. The gate and the interacting protein, L14, of the 50S ribosome act as steric filters in two consecutive substeps during accommodation, each requiring: (1) sufficient energy contained in the hybrid tRNA kink and (2) sufficient energy in the Watson–Crick base pairing of the codon–anticodon. We show that these barriers act to filter out near‐cognate tRNA and promote proofreading of the codon–anticodon. Since proofreading is essential for understanding the fidelity of translation, our model for the dynamics of this process has substantial biomedical implications. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Electrostatics of cysteine residues in proteins: Parameterization and validation of a simple model
Authors: Salsbury Freddie R. , Poole Leslie B. , Fetrow Jacquelyn S. 
Published: April 2013

AbstractOne of the most popular and simple models for the calculation of pKas from a protein structure is the semi‐macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pKas. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pKas; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pKas. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pKa values (where the calculation should reproduce the pKa within experimental error). Both the general behavior of cysteines in proteins and the perturbed pKa in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pKa should be shifted, and validation of force field parameters for cysteine residues. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Dead‐end elimination with perturbations (DEEPer): A provable protein design algorithm with continuous sidechain and backbone flexibility
Authors: Hallen Mark A. , Keedy Daniel A. , Donald Bruce R. 
Published: April 2013

AbstractComputational protein and drug design generally require accurate modeling of protein conformations. This modeling typically starts with an experimentally determined protein structure and considers possible conformational changes due to mutations or new ligands. The DEE/A* algorithm provably finds the global minimum‐energy conformation (GMEC) of a protein assuming that the backbone does not move and the sidechains take on conformations from a set of discrete, experimentally observed conformations called rotamers. DEE/A* can efficiently find the overall GMEC for exponentially many mutant sequences. Previous improvements to DEE/A* include modeling ensembles of sidechain conformations and either continuous sidechain or backbone flexibility. We present a new algorithm, DEEPer (Dead‐End Elimination with Perturbations), that combines these advantages and can also handle much more extensive backbone flexibility and backbone ensembles. DEEPer provably finds the GMEC or, if desired by the user, all conformations and sequences within a specified energy window of the GMEC. It includes the new abilities to handle arbitrarily large backbone perturbations and to generate ensembles of backbone conformations. It also incorporates the shear, an experimentally observed local backbone motion never before used in design. Additionally, we derive a new method to accelerate DEE/A*‐based calculations, indirect pruning, that is particularly useful for DEEPer. In 67 benchmark tests on 64 proteins, DEEPer consistently identified lower‐energy conformations than previous methods did, indicating more accurate modeling. Additional tests demonstrated its ability to incorporate larger, experimentally observed backbone conformational changes and to model realistic conformational ensembles. These capabilities provide significant advantages for modeling protein mutations and protein–ligand interactions. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Folding of multidomain proteins: Biophysical consequences of tethering even in apparently independent folding
Authors: Arviv Oshrit , Levy Yaakov 
Published: April 2013

AbstractMost eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering‐induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse‐grained and atomistic molecular dynamics simulations of two two‐domain constructs from the immunoglobulin‐like β‐sandwich fold. Each of these was experimentally shown to behave as the “sum of its parts,” that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two‐domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Principal component analysis of chemical shift perturbation data of a multiple‐ligand‐binding system for elucidation of respective binding mechanism
Authors: Konuma Tsuyoshi , Lee Young‐Ho , Goto Yuji , Sakurai Kazumasa 
Published: April 2013

AbstractChemical shift perturbations (CSPs) in NMR spectra provide useful information about the interaction of a protein with its ligands. However, in a multiple‐ligand‐binding system, determining quantitative parameters such as a dissociation constant (Kd) is difficult. Here, we used a method we named CS‐PCA, a principal component analysis (PCA) of chemical shift (CS) data, to analyze the interaction between bovine β‐lactoglobulin (βLG) and 1‐anilinonaphthalene‐8‐sulfonate (ANS), which is a multiple‐ligand‐binding system. The CSP on the binding of ANS involved contributions from two distinct binding sites. PCA of the titration data successfully separated the CSP pattern into contributions from each site. Docking simulations based on the separated CSP patterns provided the structures of βLG–ANS complexes for each binding site. In addition, we determined the Kd values as 3.42 × 10−4M2 and 2.51 × 10−3M for Sites 1 and 2, respectively. In contrast, it was difficult to obtain reliable Kd values for respective sites from the isothermal titration calorimetry experiments. Two ANS molecules were found to bind at Site 1 simultaneously, suggesting that the binding occurs cooperatively with a partial unfolding of the βLG structure. On the other hand, the binding of ANS to Site 2 was a simple attachment without a significant conformational change. From the present results, CS‐PCA was confirmed to provide not only the positions and the Kd values of binding sites but also information about the binding mechanism. Thus, it is anticipated to be a general method to investigate protein–ligand interactions. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Swfoldrate: Predicting protein folding rates from amino acid sequence with sliding window method
Authors: Cheng Xiang , Xiao Xuan , Wu Zhi‐cheng , Wang Pu , Lin Wei‐zhong 
Published: April 2013

AbstractProtein folding is the process by which a protein processes from its denatured state to its specific biologically active conformation. Understanding the relationship between sequences and the folding rates of proteins remains an important challenge. Most previous methods of predicting protein folding rate require the tertiary structure of a protein as an input. In this study, the long‐range and short‐range contact in protein were used to derive extended version of the pseudo amino acid composition based on sliding window method. This method is capable of predicting the protein folding rates just from the amino acid sequence without the aid of any structural class information. We systematically studied the contributions of individual features to folding rate prediction. The optimal feature selection procedures are adopted by means of combining the forward feature selection and sequential backward selection method. Using the jackknife cross validation test, the method was demonstrated on the large dataset. The predictor was achieved on the basis of multitudinous physicochemical features and statistical features from protein using nonlinear support vector machine (SVM) regression model, the method obtained an excellent agreement between predicted and experimentally observed folding rates of proteins. The correlation coefficient is 0.9313 and the standard error is 2.2692. The prediction server is freely available at http://www.jci‐bioinfo.cn/swfrate/input.jsp. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Separability between overall and internal motion: A protein folding problem
Authors: Johnson Eric 
Published: April 2013

AbstractThe separability between overall and internal motions is evaluated over multiple folding trajectories of the villin headpiece subdomain. The analysis, which relies on the Prompers‐Brüschweiler separability index, offers a potentially useful perspective on protein folding. The protein is considered folded in this study, not when it reaches some static target, but rather when it tumbles as a dynamically constrained object. The analysis also demonstrates how the separability index, when applied to protein folding simulations, can facilitate the analysis of NMR relaxation data. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Crystal structure of the Campylobacter jejuni Cj0090 protein reveals a novel variant of the immunoglobulin fold among bacterial lipoproteins
Authors: Paek Seonghee , Kawai Fumihiro , Choi Kyoung‐Jae , Yeo Hye‐Jeong 
Published: April 2013

AbstractBacterial lipoproteins play an important role in bacterial pathogenesis and physiology. The genome of Campylobacter jejuni, a major foodborn pathogen, is predicted to contain over 20 lipoproteins. However, the functions of the majority of C. jejuni lipoproteins remain unknown. The Cj0090 protein is encoded by a lipoprotein operon composed of cj0089, cj0090, and cj0091. Here, we report the crystal structure of Cj0090 at 1.9 Å resolution, revealing a novel variant of the immunoglobulin fold with β‐sandwich architecture. The structure suggests that Cj0090 may be involved in protein‐protein interactions, consistent with a possible role for bacterial lipoproteins. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Enhanced herbicide metabolism induced by 2,4‐D in herbicide susceptible Lolium rigidum provides protection against diclofop‐methyl
Authors: Han Heping , Yu Qin , Cawthray Gregory R , Powles Stephen B 
Published: April 2013

AbstractBackgroundThe auxinic herbicide 2,4‐D amine is known, in vitro, as a cytochrome P450 inducer. The current study uses 2,4‐D pre‐treatment, at the whole plant level, to study mechanism(s) of non‐target site based herbicide resistance to the ACCase‐inhibiting herbicide diclofop‐methyl in Lolium rigidum.ResultsThe 2,4‐D pre‐treatment caused up to 10‐fold shift in LD50 and GR50 in dose–response to subsequently applied diclofop‐methyl in a herbicide susceptible L. rigidum population. Foliar uptake and translocation of 14C‐diclofop‐methyl did not differ in 2,4‐D pre‐treated versus untreated plants. HPLC analysis revealed that de‐esterification of diclofop‐methyl to toxic diclofop acid was similar, but further metabolism of diclofop acid to non‐toxic metabolites was significantly (1.8‐fold) faster in 2,4‐D pre‐treated than untreated plants. HPLC profile of major polar metabolites was similar when L. rigidum and diclofop‐methyl tolerant wheat were compared, but wheat metabolised diclofop acid three‐fold faster than L. rigidum. In addition, 2,4‐D pre‐treatment also induced cross‐protection against the ALS‐inhibiting herbicide chlorsulfuron, and the known P450 inhibitor malathion can reverse this effect.ConclusionsProtection against diclofop‐methyl provided by 2,4‐D pre‐treatment in susceptible L. rigidum is associated with higher rates of herbicide metabolism, mirroring that identified in field‐evolved, non‐target site‐based diclofop‐methyl resistant populations. 2,4‐D may induce higher level expression of herbicide‐metabolising genes hence providing protection, and therefore, this 2,4‐D induction system can be used, in combination with other genomic approaches, to assist isolating cytochrome P450 and other genes that are involved in herbicide metabolism and endow herbicide resistance in L. rigidum. © 2013 Society of Chemical Industry
H ∞  preview tracking control of retarded state‐multiplicative stochastic systems
Authors: Gershon E. , Shaked U. 
Published: April 2013

SUMMARYThe problem of infinite‐horizon H ∞  state‐feedback tracking control for linear continuous time‐invariant retarded systems with stochastic parameter uncertainties is investigated. Two tracking patterns are considered depending on the nature of the reference signal; that is, whether it is measured online or previewed in a fixed time‐interval ahead. The stochastic uncertainties appear in the dynamics matrices for both the retarded and the non‐retarded states of the system. The delayed system is transformed via the input–output approach, to an uncertain norm‐bounded system. A new method that efficiently yields a min–max strategy to the solution of each of the aforementioned two cases is suggested where, given a specific reference signal, the controller plays against nature, which chooses the maximizing energy‐bounded disturbance. The theoretical results are demonstrated by two examples that show the impact of the delay length and the preview length on the system performance. Copyright © 2013 John Wiley & Sons, Ltd.
Measuring Collective Efficacy Among Children in Community‐based Afterschool Programs: Exploring Pathways toward Prevention and Positive Youth Development
Authors: Smith Emilie Phillips , Osgood D. Wayne , Caldwell Linda , Hynes Kathryn , Perkins Daniel F. 
Published: April 2013

AbstractCollective efficacy refers to a perceived sense of connectedness and willingness to intervene among youth, and is a potential aspect of positive youth development (Larson in Am Psychol 55:170–183, 2000; Lerner et al. in Child Dev 71:11–20, 2000; Sampson et al. in Science 277:918–924, 1997). Theoretically, those who feel connected to a group that is empowered to positively influence the behavior of their peers may demonstrate fewer problem behaviors. Few studies, however, have measured the impact of youth perceptions of collective efficacy. As a relatively new child‐related research topic, there is much to be learned. One contribution to the foundation of this research agenda begins by evaluating the reliability and validity of a measure of collective efficacy with elementary children attending community‐based afterschool programs. This paper describes the internal consistency reliability and various indicators of construct and concurrent validity of the Collective Efficacy Among Children Scale. The measure was found to have high internal consistency reliability. Construct validity was tested using exploratory factor analyses of collective efficacy including the dimensions of willingness to intervene and cohesion found in previous research (Sampson et al. in Science 277:918–924, 1997). Concurrent validity assessed relations between the scale and other measures in theoretically congruent ways. Using Hierarchical Linear Models to account for children's nestedness in after‐school programs, connectedness was found to be more related to emotional adjustment, particularly children's prosocial attitudes (caring about others and sharing). Children's perception of the willingness of the group to intervene was found to be related to less problem behavior, (i.e. smoking tobacco, drinking alcohol, vandalism, and stealing). The implications suggest that future research should further explore children's collective efficacy, and ways to foster its development in youth‐serving afterschool settings.