bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracheobronchopathia Osteochondroplastica in a 9‐year‐old Girl
Authors: Simsek Pelin Ozlem , Ozcelik Ugur , Demirkazik Figen , Unal Omer Faruk , Orhan Diclehan , Aslan Ayse Tana , Dogru Deniz 
Published: November 2005

AbstractTracheobroncopathia osteochondroplastica (TO) is a rare disease of adult males characterized by osteocartilagious submucosal nodules protruding into the airway lumen, causing variable degrees of airway obstruction. Here we describe a case of TO in a 9‐year‐old girl patient presenting with chronic cough, along with a brief review of this rare benign condition. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
Prevalence of Asthma among Qatari Schoolchildren: International Study of Asthma and Allergies in Childhood, Qatar
Authors: Janahi Ibrahim A. , Bener Abdulbari , Bush Andrew 
Published: November 2005

AbstractThe aim of the present study is to determine the prevalence of asthma and allergic diseases among schoolchildren aged 6–14 years in the State of Qatar, based on a questionnaire designed by the International Study of Asthma and Allergy in Childhood (ISAAC). A cross‐sectional study of 3,283 school children living in both urban and rural areas (average age, 9.03 ± 1.99 years; 52.3% boys and 47.7% girls) was conducted between February 2003–February 2004. The population sample had a high prevalence of diagnosed asthma (19.8%), allergic rhinitis (30.5%), eczema (22.5%), and chest infection (11.9%). The frequency of asthma, allergic rhinitis, and eczema among parents reflected the same pattern as seen in their children. Overall, males had more asthma, allergic rhinitis, and chest infections than females. In general, the prevalence rate of asthma and allergic rhinitis decreased with age. The prevalence rate of asthma was significantly higher in mothers (11.8%) than in fathers (9.0%), but the frequency of allergic rhinitis symptoms was comparable (mothers, 18.5%; fathers, 17.5%). The prevalence rate of asthma (19.8%) in Qatari schoolchildren is very close to that in the neighboring Gulf country, Oman (20.7%), and higher than in some developing countries. Genetic factors related to the high rates of consanguinity may play an important role in the high prevalence rates noted in the Qatari population, but changes in lifestyle and environmental factors cannot be discounted as possible causes of the high prevalence noted in this study. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
Adenotonsillectomy for Obstructive Sleep Apnea in Children with Prader‐Willi Syndrome
Authors: Pavone M. , Paglietti M.G. , Petrone A. , Crinò A. , De Vincentiis G.C. , Cutrera Renato 
Published: November 2005

AbstractThe aim of our study was to evaluate the efficacy of adenotonsillectomy for the treatment of obstructive sleep apnea syndrome (OSA) in pediatric patients with Prader‐Willi syndrome (PWS), and to describe the postoperative complications. Five patients (4 males; median age, 4.4 years; range, 1.6–14.2 years) were studied. All patients underwent an overnight cardiorespiratory sleep study. All patients had adenotonsillar hypertrophy (ATH), and two were also obese. The preoperative obstructive apnea/hypopnea index (AHI; median and range) was 12.2 (9.0–19.9) events/hr; the mean oxygen saturation was 95 (79–96)%; the nadir oxygen saturation was 71 (58–78)%; and the oxygen desaturation index (ODI) was 15.8 (11.4–35.9) events/hr. Preoperatively, patients were classified as having moderate to severe OSA. A second sleep study, performed 16 (3–43) months after adenotonsillectomy, showed a significant decrease in AHI (P = 0.009) and ODI (P = 0.009). Mean and nadir oxygen saturation did not differ significantly postsurgery (P = 0.188, P = 0.073, respectively). Four out of five children showed at least one postoperative complication. Difficult awakening from anesthesia, hemorrhages, and respiratory complications requiring reintubation and/or supplemental oxygen administration were observed. In conclusion, patients with PWS and OSA who underwent adenotonsillectomy showed a significant decrease in AHI and number of oxygen desaturations. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
The crystal structure of Aq_328 from the hyperthermophilic bacteria Aquifex aeolicus shows an ancestral histone fold
Authors: Qiu Yang , Tereshko Valentina , Kim Youngchang , Zhang Rongguang , Collart Frank , Yousef Mohammed , Kossiakoff Anthony , Joachimiak Andrzej 
Published: November 2005

AbstractThe structure of Aq_328, an uncharacterized protein from hyperthermophilic bacteria Aquifex aeolicus, has been determined to 1.9 Å by using multi‐wavelength anomalous diffraction (MAD) phasing. Although the amino acid sequence analysis shows that Aq_328 has no significant similarity to proteins with a known structure and function, the structure comparison by using the Dali server reveals that it: (1) assumes a histone‐like fold, and (2) is similar to an ancestral nuclear histone protein (PDB code 1F1E) with z‐score 8.1 and RMSD 3.6 Å over 124 residues. A sedimentation equilibrium experiment indicates that Aq_328 is a monomer in solution, with an average sedimentation coefficient of 2.4 and an apparent molecular weight of about 20 kDa. The overall architecture of Aq_328 consists of two noncanonical histone domains in tandem repeat within a single chain, and is similar to eukaryotic heterodimer (H2A/H2B and H3/H4) and an archaeal histone heterodimer (HMfA/HMfB). The sequence comparisons between the two histone domains of Aq_328 and six eukaryotic/archaeal histones demonstrate that most of the conserved residues that underlie the Aq_328 architecture are used to build and stabilize the two cross‐shaped antiparallel histone domains. The high percentage of salt bridges in the structure could be a factor in the protein's thermostability. The structural similarities to other histone‐like proteins, molecular properties, and potential function of Aq_328 are discussed in this paper. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Effect of linker segments on the stability of epithelial cadherin domain 2
Authors: Prasad Alka , Zhao Huaying , Rutherford John M. , Housley Nicole , Nichols Corey , Pedigo Susan 
Published: November 2005

AbstractEpithelial cadherin is a transmembrane protein that is essential in calcium‐dependent cell–cell recognition and adhesion. It contains five independently folded globular domains in its extracellular region. Each domain has a seven‐strand β‐sheet immunoglobulin fold. Short seven‐residue peptide segments connect the globular domains and provide oxygens to chelate calcium ions at the interface between the domains (Nagar et al., Nature 1995;380:360–364). Recently, stability studies of ECAD2 (Prasad et al., Biochemistry 2004;43:8055–8066) were undertaken with the motivation that Domain 2 is a representative domain for this family of proteins. The definition of a domain boundary is somewhat arbitrary; hence, it was important to examine the effect of the adjoining linker regions that connect Domain 2 to the adjacent domains. Present studies employ temperature–denaturation and proteolytic susceptibility to provide insight into the impact of these linkers on Domain 2. The significant findings of our present study are threefold. First, the linker segments destabilize the core domain in the absence of calcium. Second, the destabilization due to addition of the linker segments can be partially reversed by the addition of calcium. Third, sodium chloride stabilizes all constructs. This result implies that electrostatic repulsion is a contributor to destabilization of the core domain by addition of the linkers. Thus, the context of Domain 2 within the whole molecule affects its thermodynamic characteristics. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Novel statistical‐thermodynamic methods to predict protein‐ligand binding positions using probability distribution functions
Authors: Ruvinsky A. M. , Kozintsev A. V. 
Published: November 2005

AbstractWe present two novel methods to predict native protein‐ligand binding positions. Both methods identify the native binding position as the most probable position corresponding to a maximum of a probability distribution function (PDF) of possible binding positions in a protein active site. Possible binding positions are the origins of clusters composed, on the basis of root‐mean square deviations (RMSD), from the multiple ligand positions determined by a docking algorithm. The difference between the methods lies in the ways the PDF is derived. To validate the suggested methods, we compare the averaged RMSD of the predicted ligand docked positions relative to the experimentally determined positions for a set of 135 PDB protein‐ligand complexes. We demonstrate that the suggested methods improve docking accuracy by as much as 21–24% in comparison with a method that simply identifies the binding position as the energy top‐scored ligand position. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Molecular surface generation using a variable‐radius solvent probe
Authors: Bhat Sathesh , Purisima Enrico O. 
Published: November 2005

AbstractProtein–ligand binding occurs through interactions at the molecular surface. Hence, a proper description of this surface is essential to our understanding of the process of molecular recognition. Recent studies have noted the inadequacy of using a fixed 1.4 Å solvent probe radius to generate the molecular surface. This assumes that water molecules approach all surface atoms at an equal distance irrespective of polarity, which is not the case. To adequately model the protein–water boundary requires that the solvent probe radius change according to the polarity of its contacting atoms, smaller near polar atoms and larger near apolar atoms. To our knowledge, no method currently exists to generate the molecular surface of a protein in this manner. Using a modification of the marching tetrahedra algorithm, we present a method to generate molecular surfaces using a variable radius solvent probe. The resulting surface lacks many of the unrealistic small crevices in nonpolar regions that are found when utilizing an invariant 1.4 Å solvent probe, while maintaining the fine detail of the surface at polar regions. On application of the method on a test set of 20 protein structures taken from the Protein Data Bank (PDB), we also find far fewer empty unsolvated cavities that are present when using only a 1.4 Å solvent probe, while the majority of solvated and polar cavities is retained. This suggests that the majority of empty cavities previously observed in protein structures might simply be artifacts of the surfacing method. We also find that the variable probe surface can have significant effects on electrostatic calculations by generating a better tuned description of the protein–water boundary. We also examined the binding interfaces of a diverse set of 55 protein–protein complexes. We find that using a variable probe results in an increase in perceived shape complementarity at these sites compared to using a 1.4 Å solvent probe. The molecular volume and surface area are geometric values that determine various important properties for macromolecules, and the altered description afforded by a variable solvent probe molecular surface can have significant implications in protein recognition, energetics, folding, and stability calculations. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Divalent ion‐binding properties of the two avian β‐parvalbumins
Authors: Henzl Michael T. , Agah Sayeh 
Published: November 2005

AbstractBirds express three parvalbumins, one α isoform and two β isoforms. The latter are known as avian thymic hormone (ATH) and avian parvalbumin 3. Although both were discovered in thymus tissue, and presumably function in T‐cell maturation, they have been detected in other tissue settings. We have conducted detailed Ca2+‐ and Mg2+‐binding studies on recombinant ATH and the C72S variant of CPV3, employing global analysis of isothermal titration calorimetry data. In Hepes‐buffered saline, ATH binds Ca2+with apparent microscopic binding constants of 2.4 ± 0.2 × 108and 1.0 ± 0.1 × 108M−1. The corresponding values for CPV3‐C72S are substantially lower, 4.5 ± 0.5 × 107and 2.4 ± 0.2 × 107M−1, a 1.9‐kcal/mol difference in binding free energy. Thus, the β‐parvalbumin lineage displays a spectrum of Ca2+‐binding affinity, with ATH and the mammalian β isoform at the high‐ and low‐affinity extremes and CPV3 in the middle. Interestingly, despite its decreased Ca2+affinity, CPV3‐C72S exhibits increased affinity for Mg2+, relative to ATH. Whereas the latter displays Mg2+‐binding constants of 2.2 ± 0.2 × 104and 1.2 ± 0.1 × 104M−1, CPV3‐C72S yields values of 5.0 ± 0.8 × 104and 2.1 ± 0.3 × 104M−1. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Crystal structure of a heterodimer of phospholipase A2 from Naja naja sagittifera at 2.3 Å resolution reveals the presence of a new PLA2‐like protein with a novel cys 32–Cys 49 disulphide bridge with a bound sugar at the substrate‐binding site
Authors: Jabeen Talat , Singh Nagendra , Singh Rajendra K. , Jasti Jayasankar , Sharma Sujata , Kaur Punit , Srinivasan Alagiri , Singh Tej P. 
Published: November 2005

AbstractThe crystal structure of the phospholipase A2 (PLA2) heterodimer from Naja naja sagittifera reveals the presence of a new PLA2‐like protein with eight disulphide bridges. The heterodimer is formed between a commonly observed group I PLA2 having seven characteristic disulfide bonds and a novel PLA2‐like protein (Cys–PLA2) containing two extra cysteines at two highly conserved sites (positions 32 and 49) of structural and functional importantance. The crystals of the heterodimer belong to tetragonal space group P41212 with cell dimensions, a = b = 77.7 Å and c = 68.4 Å corresponding to a solvent content of 33%, which is one of the lowest values observed so far in the PLA2 crystals. The structure has been solved with molecular replacement method and refined to a final R value of 21.6% [Rfree = 25.6%]. The electron density revealed the presence of cysteines 32 and 49 that are covalently linked to give rise to an eighth disulphide bridge in the PLA2‐like monomer. A non‐protein high‐quality electron density was also observed at the substrate‐binding site in the PLA2‐like protein that has been interpreted as N‐acetylglucosamine. The overall tertiary folds of the two monomers are similar having all features of PLA2‐type folding. A zinc ion is detected at the interface of the heterodimer with fivefold coordination while another zinc ion was found on the surface of Cys–PLA2 with sixfold coordination. The conformations of the calcium‐binding loops of both monomers are significantly different from each other as well as from those in other group I PLA2s. The N‐acetylglucosamine molecule is favorably placed in the substrate‐binding site of Cys–PLA2 and forms five hydrogen bonds and several van der Waals interactions with protein atoms, thus indicating a strong affinity. It also provides clue of the possible mechanism of sugar recognition by PLA2 and PLA2‐like proteins. The formation of heterodimer seems to have been induced by zinc ion. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Folding pathway dependence on energetic frustration and interaction heterogeneity for a three‐dimensional hydrophobic protein model
Authors: Garcia Leandro G. , Pereira de Araújo Antônio F. 
Published: November 2005

AbstractMonte Carlo simulations of a hydrophobic protein model of 40 monomers in the cubic lattice are used to explore the effect of energetic frustration and interaction heterogeneity on its folding pathway. The folding pathway is described by the dependence of relevant conformational averages on an appropriate reaction coordinate, pfold, defined as the probability for a given conformation to reach the native structure before unfolding. We compare the energetically frustrated and heterogeneous hydrophobic potential, according to which individual monomers have a higher or lower tendency to form contacts unspecifically depending on their hydrophobicities, to an unfrustrated homogeneous Go‐type potential with uniformly attractive native interactions and neutral non‐native interactions (called Go1 in this study), and to an unfrustrated heterogeneous potential with neutral non‐native interactions and native interactions having the same energy as the hydrophobic potential (called Go2 in this study). Folding kinetics are slowed down dramatically when energetic frustration increases, as expected and previously observed in a two‐dimensional model. Contrary to our previous results in two dimensions, however, it appears that the folding pathway and transition state ensemble can be significantly dependent on the energy function used to stabilize the native structure. The sequence of events along the reaction coordinate, or the order along this coordinate in which different regions of the native conformation become structured, turns out to be similar for the hydrophobic and Go2 potentials, but with analogous events tending to occur at lower pfold values in the first case. In particular, the transition state obtained from the ensemble around pfold = 0.5 is more structured for the hydrophobic potential. For Go1, not only the transition state ensemble but the order of events itself is modified, suggesting that interaction heterogeneity, in addition to energetic frustration, can have significant effects on the folding mechanism, most likely by modifying the probability of different contacts in the unfolded state, the starting point for the folding reaction. Although based on a simple model, these results provide interesting insight into how sequence‐dependent switching between folding pathways might occur in real proteins. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Computational characterization of the sequence landscape in simple protein alphabets
Authors: Shell M. Scott , Debenedetti Pablo G. , Panagiotopoulos Athanassios Z. 
Published: November 2005

AbstractWe characterize the “sequence landscapes” in several simple, heteropolymer models of proteins by examining their mutation properties. Using an efficient flat‐histogram Monte Carlo search method, our approach involves determining the distribution in energy of all sequences of a given length when threaded through a common backbone. These calculations are performed for a number of Protein Data Bank structures using two variants of the 20‐letter contact potential developed by Miyazawa and Jernigan [Miyazawa S, Jernigan WL. Macromolecules 1985;18:534], and the 2‐monomer HP model of Lau and Dill [Lau KF, Dill KA. Macromolecules 1989;22:3986]. Our results indicate significant differences among the energy functions in terms of the “smoothness” of their landscapes. In particular, one of the Miyazawa‐Jernigan contact potentials reveals unusual cooperative behavior among its species' interactions, resulting in what is essentially a set of phase transitions in sequence space. Our calculations suggest that model‐specific features can have a profound effect on protein design algorithms, and our methods offer a number of ways by which sequence landscapes can be quantified. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Conserved quantitative stability/flexibility relationships (QSFR) in an orthologous RNase H pair
Authors: Livesay Dennis R. , Jacobs Donald J. 
Published: November 2005

AbstractMany reports qualitatively describe conserved stability and flexibility profiles across protein families, but biophysical modeling schemes have not been available to robustly quantify both. Here we investigate an orthologous RNase H pair by using a minimal distance constraint model (DCM). The DCM is an all atom microscopic model [Jacobs and Dallakyan, Biophys J 2005;88(2):903–915] that accurately reproduces heat capacity measurements [Livesay et al., FEBS Lett 2004;576(3):468–476], and is unique in its ability to harmoniously calculate thermodynamic stability and flexibility in practical computing times. Consequently, quantified stability/flexibility relationships (QSFR) can be determined using the DCM. For the first time, a comparative QSFR analysis is performed, serving as a paradigm study to illustrate the utility of a QSFR analysis for elucidating evolutionarily conserved stability and flexibility profiles. Despite global conservation of QSFR profiles, distinct enthalpy‐entropy compensation mechanisms are identified between the RNase H pair. In both cases, local flexibility metrics parallel H/D exchange experiments by correctly identifying the folding core and several flexible regions. Remarkably, at appropriately shifted temperatures (e.g., melting temperature), these differences lead to a global conservation in Landau free energy landscapes, which directly relate thermodynamic stability to global flexibility. Using ensemble‐based sampling within free energy basins, rigidly, and flexibly correlated regions are quantified through cooperativity correlation plots. Five conserved flexible regions are identified within the structures of the orthologous pair. Evolutionary conservation of these flexibly correlated regions is strongly suggestive of their catalytic importance. Conclusions made herein are demonstrated to be robust with respect to the DCM parameterization. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Ensemble‐based signatures of energy propagation in proteins: A new view of an old phenomenon
Authors: Liu Tong , Whitten Steven T. , Hilser Vincent J. 
Published: November 2005

AbstractThe ability of a protein to transmit the energetic effects of binding from one site to another constitutes the underlying basis for allosterism and signal transduction. Despite clear experimental evidence indicating the ability of proteins to transmit the effects of binding, the means by which this propagation is facilitated is not well understood. Using our previously developed ensemble‐based description of the equilibrium, we investigated the physical basis of energy propagation and identified several fundamental and general aspects of energetic coupling between residues in a protein. First, partitioning of a conformational ensemble into four distinct sub‐ensembles allows for explanation of the range of experimentally observed coupling behaviors (i.e., positive, neutral, and negative coupling between various regions of the protein structure). Second, the relative thermodynamic properties of these four sub‐ensembles define the energetic coupling between residues as either positive, neutral, or negative. Third, analysis of the structural and thermodynamic features of the states within each sub‐ensemble reveals significant variability. This third result suggests that a quantitative description of energy propagation in proteins requires an understanding of the structural and energetic features of more than just one or a few low‐energy states, but also of many high‐energy states. Such findings illuminate the difficulty in interpreting energy propagation in proteins in terms of a structural pathway that physically links coupled sites. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Assessing protein disorder and induced folding
Authors: Receveur‐Bréchot Véronique , Bourhis Jean‐Marie , Uversky Vladimir N. , Canard Bruno , Longhi Sonia 
Published: November 2005

AbstractIntrinsically disordered proteins (IDPs) defy the structure–function paradigm as they fulfill essential biological functions while lacking well‐defined secondary and tertiary structures. Conformational and spectroscopic analyses showed that IDPs do not constitute a uniform family, and can be divided into subfamilies as a function of their residual structure content. Residual intramolecular interactions are thought to facilitate binding to a partner and then induced folding. Comprehensive information about experimental approaches to investigate structural disorder and induced folding is still scarce. We herein provide hints to readily recognize features typical of intrinsic disorder and review the principal techniques to assess structural disorder and induced folding. We describe their theoretical principles and discuss their respective advantages and limitations. Finally, we point out the necessity of using different approaches and show how information can be broadened by the use of multiples techniques. Proteins 2006. © 2005 Wiley‐Liss, Inc.