bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence and structure of epoxide hydrolases: A systematic analysis
Authors: Barth Sandra , Fischer Markus , Schmid Rolf D. , Pleiss Jürgen 
Published: April 2004

AbstractEpoxide hydrolases (EC 3.3.2.3) are ubiquitous enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. More than 100 epoxide hydrolases (EH) have been identified or predicted, and 3 structures are available. Although they catalyze the same chemical reaction, sequence similarity is low. To identify conserved regions, all EHs were aligned. Phylogenetic analysis identified 12 homologous families, which were grouped into 2 major superfamilies: the microsomal EH superfamily, which includes the homologous families of Mammalian, Insect, Fungal, and Bacterial EHs, and the cytosolic EH superfamily, which includes Mammalian, Plant, and Bacterial EHs. Bacterial EHs show a high sequence diversity. Based on structure comparison of three known structures from Agrobacterium radiobacter AD1 (cytosolic EH), Aspergillus niger (microsomal EH), Mus musculus (cytosolic EH), and multisequence alignment and phylogenetic analysis of 95 EHs, the modular architecture of this enzyme family was analyzed. Although core and cap domain are highly conserved, the structural differences between the EHs are restricted to only two loops: the NC‐loop connecting the core and the cap and the cap‐loop, which is inserted into the cap domain. EHs were assigned to either of three clusters based on loop length. By using this classification, core and cap region of all EHs, NC‐loops and cap‐loops of 78% and 89% of all EHs, respectively, could be modeled. Representative models are available from the Lipase Engineering Database, http://www.led.uni‐stuttgart.de. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
An unusual triosephosphate isomerase from the early divergent eukaryote Giardia lamblia
Authors: López‐Velázquez Gabriel , Molina‐Ortiz Dora , Cabrera Nallely , Hernández‐Alcántara Gloria , Peon‐Peralta Jorge , Yépez‐Mulia Lilian , Pérez‐Montfort Ruy , Reyes‐Vivas Horacio 
Published: April 2004

AbstractRecombinant triosephosphate isomerase from the parasite Giardia lamblia (GlTIM) was characterized and immunolocalized. The enzyme is distributed uniformly throughout the cytoplasm. Size exclusion chromatography of the purified enzyme showed two peaks with molecular weights of 108 and 55 kDa. Under reducing conditions, only the 55‐kDa protein was detected. In denaturing gel electrophoresis without dithiothreitol, the enzyme showed two bands with molecular weights of 28 and 50 kDa; with dithiotretitol, only the 28‐kDa protein was observed. These data indicate that GlTIM may exist as a tetramer or a dimer and that, in the former, the two dimers are covalently linked by disulfide bonds. The kinetics of the dimer were similar to those of other TIMs. The tetramer exhibited half of the kcat of the dimer without changes in the Km. Studies on the thermal stability and the apparent association constants between monomers showed that the tetramer was slightly more stable than the dimer. This finding suggests the oligomerization is not related to enzyme thermostability as in Thermotoga maritima. Instead, it could be that oligomerization is related to the regulation of catalytic activity in different states of the life cycle of this mesophilic parasite. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Superfamily active site templates
Authors: Meng Elaine C. , Polacco Benjamin J. , Babbitt Patricia C. 
Published: April 2004

AbstractWe show that three‐dimensional signatures consisting of only a few functionally important residues can be diagnostic of membership in superfamilies of enzymes. Using the enolase superfamily as a model system, we demonstrate that such a signature, or template, can identify superfamily members in structural databases with high sensitivity and specificity. This is remarkable because superfamilies can be highly diverse, with members catalyzing many different overall reactions; the unifying principle can be a conserved partial reaction or chemical capability. Our definition of a superfamily thus hinges on the disposition of residues involved in a conserved function, rather than on fold similarity alone. A clear advantage of basing structure searches on such active site templates rather than on fold similarity is the specificity with which superfamilies with distinct functional characteristics can be identified within a large set of proteins with the same fold, such as the (β/α)8 barrels. Preliminary results are presented for an additional group of enzymes with a different fold, the haloacid dehalogenase superfamily, suggesting that this approach may be generally useful for assigning reading frames of unknown function to specific superfamilies and thereby allowing inference of some of their functional properties. Proteins 2004;9999:000–000. © 2004 Wiley‐Liss, Inc.
Relationships between amino acid sequence and backbone torsion angle preferences
Authors: Keskin O. , Yuret D. , Gursoy A. , Turkay M. , Erman B. 
Published: April 2004

AbstractStatistical averages and correlations for backbone torsion angles of chymotrypsin inhibitor 2 are calculated by using the Rotational Isomeric States model of chain statistics. Statistical weights of torsional states of ϕψ pairs, needed for the statistics of the full chain, are obtained in two different ways: 1) by using knowledge‐based pairwise dependent ϕψ energy maps from Protein Data Bank (PDB) and 2) by collecting torsion angle data from a large number of random coil configurations of an all‐atom protein model with volume exclusion. Results obtained by using PDB data show strong correlations between adjacent torsion angle pairs belonging to both the same and different residues. These correlations favor the choice of the native‐state torsion angles, and they are strongly context dependent, determined by the specific amino acid sequence of the protein. Excluded volume or steric clashes, only, do not introduce context‐dependent ϕψ correlations into the chain that would affect the choice of native‐state torsional angles. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels
Authors: Frénal Karine , Xu Chen‐Qi , Wolff Nicolas , Wecker Karine , Gurrola Georgina B. , Zhu Shun‐Yi , Chi Cheng‐Wu , Possani Lourival D. , Tytgat Jan , Delepierre Muriel 
Published: April 2004

AbstractThe γ‐KTx–type scorpion toxins specific for K+ channels were found to interact with ERG channels on the turret region, while α‐KTx3.2 Agitoxin‐2 binds to the pore region of the Shaker K+ channel, and α‐KTx5.3 BmP05 binds to the intermediate region of the small‐conductance calcium‐activated K‐channel (SKCa). In order to explore the critical residues for γ‐KTx binding, we determined the NMR structure of native γ‐KTx1.1 (CnErg1), a 42 amino acid residues scorpion toxin isolated from the venom of the Mexican scorpion Centruroïdes noxius Hoffmann, and we used computational evolutionary trace (ET) analysis to predict possible structural and functional features of interacting surfaces. The 1H‐NMR three‐dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3JNH‐Hα and 10 hydrogen bonds. The structure is characterized by 2 segments of α‐helices and a triple‐stranded antiparallel β‐sheet stabilized by 4 disulfide bridges. The ET and structural analysis provided indication of the presence of two important amino acid residue clusters, one hydrophobic and the other hydrophilic, that should be involved in the surface contact between the toxin and the channel. Some features of the proposed interacting surface are discussed. Proteins 2004. © 2004 Wiley‐Liss, Inc.
YbdK is a carboxylate‐amine ligase with a γ‐glutamyl:Cysteine ligase activity: Crystal structure and enzymatic assays
Authors: Lehmann Christopher , Doseeva Victoria , Pullalarevu Sadhana , Krajewski Wojciech , Howard Andrew , Herzberg Osnat 
Published: April 2004

AbstractThe Escherichia coli open reading frame YbdK encodes a member of a large bacterial protein family of unknown biological function. The sequences within this family are remotely related to the sequence of γ‐glutamate‐cysteine ligase (γ‐GCS), an enzyme in the glutathione biosynthetic pathway. A gene encoding γ‐GCS in E. coli is already known. The 2.15 Å resolution crystal structure of YbdK reveals an overall fold similar to that of glutamine synthetase (GS), a nitrogen metabolism enzyme that ligates glutamate and ammonia to yield glutamine. GS and γ‐GCS perform related chemical reactions and require ATP and Mg2+ for their activity. The Mg2+‐dependent binding of ATP to YbdK was confirmed by fluorescence spectroscopy employing 2′(or 3′)‐O‐(trinitrophenyl)adenosine 5′‐triphosphate, and yielding a dissociation constant of 3 ± 0.5 μM. The structure of YbdK contains a crevice that corresponds to the binding sites of ATP, Mg2+ and glutamate in GS. Many of the GS residues that coordinate the metal ions and interact with glutamic acid and the phosphoryl and ribosyl groups of ATP are also present in YbdK. GS amino acids that have been associated with ammonia binding have no obvious counterparts in YbdK, consistent with a substrate specificity that is different from that of GS. Ligase activity between glutamic acid and each of the twenty amino acid residues was tested on high performance liquid chromatography (HPLC) by following the hydrolysis of ATP to ADP. Catalysis was observed only with cysteine. A pyruvate kinase/lactic acid dehydrogenase coupled assay was used to rule out GS activity and to determine that YbdK exhibits γ‐GCS activity. The catalytic rate was found to be approximately 500‐fold slower than that reported for authentic γ‐GCS. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Calculating proton uptake/release and binding free energy taking into account ionization and conformation changes induced by protein–inhibitor association: Application to plasmepsin, cathepsin D and endothiapepsin–pepstatin complexes
Authors: Alexov Emil 
Published: April 2004

AbstractThe protein‐inhibitor binding energies of enzymes are often pH dependent, and binding induces either proton uptake or proton release. The proton uptake/release and the binding energy for three complexes with available experimental data were numerically studied: pepstatin–cathepsin D, pepstatin–plasmepsin II and pepstatin–endothiapepsin. Very good agreement with the experimental data was achieved when conformational changes were taken into account. The role of the desolvation energy and the conformational changes was revealed by modeling the complex, the separated molecules in the complex conformation and the free molecules. It was shown that the conformational changes induced by the complex formation are as important for the proton transfer as the loss of solvation energy caused by the burial of interface residues. The residues responsible for the proton transfer were identified and their contribution to the proton uptake/release calculated. These residues were found to be scattered along the whole protein rather than being localized only at the active site. In the case of cathepsin D, these residues were found to be highly conserved among the cathepsin D sequences of other species. It was shown that conformation and ionization changes induced by the complex formation are critical for the correct calculation of the binding energy. Taking into account the electrostatics and the van der Waals (vdW) energies within the Boltzmann distribution of energies and allowing ionization and conformation changes to occur makes the calculated binding energy more realistic and closer to the experimental value. The interplay between electrostatic and vdW forces makes the pH dependence of the binding energy smoother, because the vdW force acts in reaction to the changes of the electrostatic energy. It was found that a small fraction of the ionizable groups remain uncharged in both the free and complexed molecules. The sequence and structural position of these groups aligns well within the three proteases, suggesting that these may have specific role. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Towards a structural classification of phosphate binding sites in protein–nucleotide complexes: An automated all‐against‐all structural comparison using geometric matching
Authors: Brakoulias Andreas , Jackson Richard M. 
Published: April 2004

AbstractA method is described for the rapid comparison of protein binding sites using geometric matching to detect similar three‐dimensional structure. The geometric matching detects common atomic features through identification of the maximum common sub‐graph or clique. These features are not necessarily evident from sequence or from global structural similarity giving additional insight into molecular recognition not evident from current sequence or structural classification schemes. Here we use the method to produce an all‐against‐all comparison of phosphate binding sites in a number of different nucleotide phosphate‐binding proteins. The similarity search is combined with clustering of similar sites to allow a preliminary structural classification. Clustering by site similarity produces a classification of binding sites for the 476 representative local environments producing ten main clusters representing half of the representative environments. The similarities make sense in terms of both structural and functional classification schemes. The ten main clusters represent a very limited number of unique structural binding motifs for phosphate. These are the structural P‐loop, di‐nucleotide binding motif [FAD/NAD(P)‐binding and Rossman‐like fold] and FAD‐binding motif. Similar classification schemes for nucleotide binding proteins have also been arrived at independently by others using different methods. Proteins 2004. © 2004 Wiley‐Liss, Inc.
β‐Hairpin folding and stability: molecular dynamics simulations of designed peptides in aqueous solution
Authors: Santiveri Clara M. , Jiménez M. Ángeles , Rico Manuel , van Gunsteren Wilfred F. , Daura Xavier 
Published: April 2004

AbstractThe structural properties of a 10‐residue and a 15‐residue peptide in aqueous solution were investigated by molecular dynamics simulation. The two designed peptides, SYINSDGTWT and SESYINSDGTWTVTE, had been studied previously by NMR at 278 K and the resulting model structures were classified as 3:5 β‐hairpins with a type I + G1 β‐bulge turn. In simulations at 278 K, starting from the NMR model structure, the 3:5 β‐hairpin conformers proved to be stable over the time period evaluated (30 ns). Starting from an extended conformation, simulations of the decapeptide at 278 K, 323 K and 353 K were also performed to study folding. Over the relatively short time scales explored (30 ns at 278 K and 323 K, 56 ns at 353 K), folding to the 3:5 β‐hairpin could only be observed at 353 K. At this temperature, the collapse to β‐hairpin‐like conformations is very fast. The conformational space accessible to the peptide is entirely dominated by loop structures with different degrees of β‐hairpin character. The transitions between different types of ordered loops and β‐hairpins occur through two unstructured loop conformations stabilized by a single side‐chain interaction between Tyr2 and Trp9, which facilitates the changes of the hydrogen‐bond register. In agreement with previous experimental results, β‐hairpin formation is initially driven by the bending propensity of the turn segment. Nevertheless, the fine organization of the turn region appears to be a late event in the folding process. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Tissue distribution of antihypertensive dipeptide, Val‐Tyr, after its single oral administration to spontaneously hypertensive rats
Authors: Matsui Toshiro , Imamura Miho , Oka Hiromi , Osajima Katsuhiro , Kimoto Ko‐Ichi , Kawasaki Terukazu , Matsumoto Kiyoshi 
Published: April 2004

AbstractThe distribution of an antihypertensive dipeptide, Val‐Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18‐week‐old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h198.0 ± 3.6 mmHg; SBP9h 154.6 ± 3.5 mmHg). As a result of VY determination, a roughly 10‐fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I‐converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Interval Charting Schemes for Joint Monitoring of Process Mean and Variance
Authors: Gan F. F. , Ting K. W. , Chang T. C. 
Published: April 2004

AbstractShewhart mean and variance schemes continue to enjoy great popularity among process engineers because they are easy to understand and are the most sensitive in detecting large process shifts. For some processes, for example the screen printing process in memory modules assembly, there is a possibility of the process mean and variance shifting at the same time due to special causes. Thus, instead of studying the joint behavior by looking at the mean and variance information on two separate charts, it is practical and usually more meaningful to look at the combined mean and variance information on an interval charting scheme. The interval scheme is found to have a similar run length performance to the Shewhart mean and variance schemes and only a single chart needs to be managed. A simple design procedure for the interval scheme that matches the corresponding Shewhart scheme is provided for easy implementation. Also, the interval and Shewhart schemes are compared based on real manufacturing data sets. Copyright © 2004 John Wiley & Sons, Ltd.
JaRec: a portable record/replay environment for multi‐threaded Java applications
Authors: Georges A. , Christiaens M. , Ronsse M. , De Bosschere K. 
Published: April 2004

AbstractThis paper describes JaRec, a portable record/replay system for Java. It correctly replays multi‐threaded, data‐race free Java applications, by recording the order of synchronization operations, and by executing them in the same order during replay. The record/replay infrastructure is developed in Java, and does not require a modification of the Java Virtual Machine (JVM) if it provides the JVM Profiler Interface (JVMPI). If the JVM does not support JVMPI, which is used for intercepting the loaded classes, only a minor modification to the JVM is required in order to run the system. On ystems with limited memory resources, JaRec can be executed in a distributed fashion. This also makes it suitable to aid debugging of multi‐threaded applications on embedded systems. Copyright © 2004 John Wiley & Sons, Ltd.
A Web‐based distributed system for hurricane occurrence projection
Authors: Chen Shu‐Ching , Gulati Sneh , Hamid Shahid , Huang Xin , Luo Lin , Morisseau‐Leroy Nirva , Powell Mark D. , Zhan Chengjun , Zhang Chengcui 
Published: April 2004

AbstractAs an environmental phenomenon, hurricanes cause significant property damage and loss of life in coastal areas almost every year. Research concerning hurricanes and their aftermath is gaining more and more attention nowadays. This paper presents our work in designing and building a Web‐based distributed software system that can be used for the statistical analysis and projection of hurricane occurrences. Firstly, our system is a large‐scale system and can handle the huge amount of hurricane data and intensive computations in hurricane data analysis and projection. Secondly, it is a distributed system, which allows multiple users at different locations to access the system simultaneously and to share and exchange the data and data model. Thirdly, our system is a database‐centered system where the Oracle database is employed to store and manage the large amount of hurricane data, the hurricane model and the projection results. Finally, a three‐tier architecture has been adopted to make our system robust and resistant to the potential change in the lifetime of the system. This paper focuses on the three‐tier system architecture, describing the design and implementation of the components at each layer. Copyright © 2004 John Wiley & Sons, Ltd.
Tracing system‐level communication in distributed systems
Authors: Mann Zoltán Ádám , Kondorosi Károly 
Published: April 2004

AbstractTraditional tracing mechanisms, usually developed for use in a single‐computer environment, are bound to a specific programming language. Today's highly distributed and heterogeneous computing environments require new tracing methodologies. This paper addresses the problem by reviewing ways in which the middleware might—and should—support tracing. In particular, CORBA (Common Object Request Broker Architecture) meta‐objects that can be applied for tracing are studied. One meta‐object, namely the interceptor concept, is presented in more depth, followed by a detailed description of an interceptor‐based tracing architecture for CORBA applications. Implementation details and evaluation experience are given. Copyright © 2004 John Wiley & Sons, Ltd.
A softerware monitor for shared‐memory multiprocessor computers
Authors: Liu Xian , Xu Feilong 
Published: April 2004

AbstractANIX is a multiprocessor operating system to be used in the backbone Asynchronous Transfer Mode (ATM) switches. In ANIX, memory contention by processes running on different CPUs is managed with a protocol called WWWH (when to sleep, who to sleep, where to sleep, and how to sleep). Tools are needed to test, debug, and tune the system running WWWH. This paper describes the experience and practice in design of SHMON, a performance tool that monitors the dynamic behavior of the running system. Copyright © 2004 John Wiley & Sons, Ltd.