bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐body residue‐level knowledge‐based energy score combined with sequence‐profile and secondary structure information for fold recognition
Authors: Zhou Hongyi , Zhou Yaoqi 
Published: April 2004

AbstractAn elaborate knowledge‐based energy function is designed for fold recognition. It is a residue‐level single‐body potential so that highly efficient dynamic programming method can be used for alignment optimization. It contains a backbone torsion term, a buried surface term, and a contact‐energy term. The energy score combined with sequence profile and secondary structure information leads to an algorithm called SPARKS (Sequence, secondary structure Profiles and Residue‐level Knowledge‐based energy Score) for fold recognition. Compared with the popular PSI‐BLAST, SPARKS is 21% more accurate in sequence‐sequence alignment in ProSup benchmark and 10%, 25%, and 20% more sensitive in detecting the family, superfamily, fold similarities in the Lindahl benchmark, respectively. Moreover, it is one of the best methods for sensitivity (the number of correctly recognized proteins), alignment accuracy (based on the MaxSub score), and specificity (the average number of correctly recognized proteins whose scores are higher than the first false positives) in LiveBench 7 among more than twenty servers of non‐consensus methods. The simple algorithm used in SPARKS has the potential for further improvement. This highly efficient method can be used for fold recognition on genomic scales. A web server is established for academic users on http://theory.med.buffalo.edu. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Ultrahigh resolution drug design I: Details of interactions in human aldose reductase–inhibitor complex at 0.66 Å
Authors: Howard E.I. , Sanishvili R. , Cachau R.E. , Mitschler A. , Chevrier B. , Barth P. , Lamour V. , Van Zandt M. , Sibley E. , Bon C. , Moras D. , Schneider T.R. , Joachimiak A. , Podjarny A. 
Published: April 2004

AbstractThe first subatomic resolution structure of a 36 kDa protein [aldose reductase (AR)] is presented. AR was cocrystallized at pH 5.0 with its cofactor NADP+ and inhibitor IDD 594, a therapeutic candidate for the treatment of diabetic complications. X‐ray diffraction data were collected up to 0.62 Å resolution and treated up to 0.66 Å resolution. Anisotropic refinement followed by a blocked matrix inversion produced low standard deviations (<0.005 Å). The model was very well ordered overall (CA atoms' mean B factor is 5.5 Å2). The model and the electron‐density maps revealed fine features, such as H‐atoms, bond densities, and significant deviations from standard stereochemistry. Other features, such as networks of hydrogen bonds (H bonds), a large number of multiple conformations, and solvent structure were also better defined. Most of the atoms in the active site region were extremely well ordered (mean B ∼3 Å2), leading to the identification of the protonation states of the residues involved in catalysis. The electrostatic interactions of the inhibitor's charged carboxylate head with the catalytic residues and the charged coenzyme NADP+ explained the inhibitor's noncompetitive character. Furthermore, a short contact involving the IDD 594 bromine atom explained the selectivity profile of the inhibitor, important feature to avoid toxic effects. The presented structure and the details revealed are instrumental for better understanding of the inhibition mechanism of AR by IDD 594, and hence, for the rational drug design of future inhibitors. This work demonstrates the capabilities of subatomic resolution experiments and stimulates further developments of methods allowing the use of the full potential of these experiments. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV‐1 protease
Authors: Vega Sonia , Kang Lin‐Woo , Velazquez‐Campoy Adrian , Kiso Yoshiaki , Amzel L. Mario , Freire Ernesto 
Published: April 2004

AbstractThe efficacy of HIV‐1 protease inhibition therapies is often compromised by the appearance of mutations in the protease molecule that lower the binding affinity of inhibitors while maintaining viable catalytic activity and substrate affinity. The V82F/I84V double mutation is located within the binding site cavity and affects all protease inhibitors in clinical use. KNI‐764, a second‐generation inhibitor currently under development, maintains significant potency against this mutation by entropically compensating for enthalpic losses, thus minimizing the loss in binding affinity. KNI‐577 differs from KNI‐764 by a single functional group critical to the inhibitor response to the protease mutation. This single difference changes the response of the two inhibitors to the mutation by one order of magnitude. Accordingly, a structural understanding of the inhibitor response will provide important guidelines for the design of inhibitors that are less susceptible to mutations conveying drug resistance. The structures of the two compounds bound to the wild type and V82F/I84V HIV‐1 protease have been determined by X‐ray crystallography at 2.0 Å resolution. The presence of two asymmetric functional groups, linked by rotatable bonds to the inhibitor scaffold, allows KNI‐764 to adapt to the mutated binding site cavity more readily than KNI‐577, with a single asymmetric group. Both inhibitors lose about 2.5 kcal/mol in binding enthalpy when facing the drug‐resistant mutant protease; however KNI‐764 gains binding entropy while KNI‐577 loses binding entropy. The gain in binding entropy by KNI‐764 accounts for its low susceptibility to the drug‐resistant mutation. The heat capacity change associated with binding becomes more negative when KNI‐764 binds to the mutant protease, consistent with increased desolvation. With KNI‐577, the opposite effect is observed. Structurally, the crystallographic B factors increase for KNI‐764 when it is bound to the drug‐resistant mutant. The opposite is observed for KNI‐577. Consistent with these observations, it appears that KNI‐764 is able to gain binding entropy by a two‐fold mechanism: it gains solvation entropy by burying itself deeper within the binding pocket and gains conformational entropy by losing interaction with the protease. Proteins 2004. © 2004 Wiley‐Liss, Inc.
The emergence of catalytic and structural diversity within the beta‐clip fold
Authors: Iyer Lakshminarayan M. , Aravind L. 
Published: April 2004

AbstractThe β‐clip fold includes a diverse group of protein domains that are unified by the presence of two characteristic waist‐like constrictions, which bound a central extended region. Members of this fold include enzymes like deoxyuridine triphosphatase and the SET methylase, carbohydrate‐binding domains like the fish antifreeze proteins/Sialate synthase C‐terminal domains, and functionally enigmatic accessory subunits of urease and molybdopterin biosynthesis protein MoeA. In this study, we reconstruct the evolutionary history of this fold using sensitive sequence and structure comparisons methods. Using sequence profile searches, we identified novel versions of the β‐clip fold in the bacterial flagellar chaperone FlgA and the related pilus protein CpaB, the StrU‐like dehydrogenases, and the UxaA/GarD‐like hexuronate dehydratases (SAF superfamily). We present evidence that these versions of the β‐clip domain, like the related type III anti‐freeze proteins and C‐terminal domains of sialic acid synthases, are involved in interactions with carbohydrates. We propose that the FlgA and CpaB‐like proteins mediate the assembly of bacterial flagella and Flp pili by means of their interactions with the carbohydrate moieties of peptidoglycan. The N‐terminal β‐clip domain of the hexuronate dehydratases appears to have evolved a novel metal‐binding site, while their C‐terminal domain is likely to adopt a metal‐binding TIM barrel‐like fold. Using structural comparisons, we show that the β‐clip fold can be further classified into two major groups, one that includes the SAF, SET, dUTPase superfamilies, and the other that includes the phage lambda head decoration protein, the β subunit of urease and the C‐terminal domain of the molybdenum cofactor biosynthesis protein MoeA. Structural comparisons also suggest the β‐clip fold was assembled through the duplication of a three‐stranded unit. Though the three‐stranded units are likely to have had a common origin, we present evidence that complete β‐clip domains were assembled through such duplications, independently on multiple occasions. There is also evidence for circular permutation of the basic three‐stranded unit on different occasions in the evolution of the β‐clip unit. We also describe how assembly of this fold from a basic three‐stranded unit has been utilized to accommodate a variety of activities in its different versions. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Protein–water interactions in ribonuclease A and angiogenin: A molecular dynamics study
Authors: Sanjeev B. S. , Vishveshwara S. 
Published: April 2004

AbstractIt is known that water molecules play an important role in the biological functioning of proteins. The members of the ribonuclease A (RNase A) family of proteins, which are sequentially and structurally similar, are known to carry out the obligatory function of cleaving RNA and individually perform other diverse biological functions. Our focus is on elucidating whether the sequence and structural similarity lead to common hydration patterns, what the common hydration sites are and what the differences are. Extensive molecular dynamics simulations followed by a detailed analysis of protein–water interactions have been carried out on two members of the ribonuclease A superfamily—RNase A and angiogenin. The water residence times are analyzed and their relationship with the characteristic properties of the protein polar atoms, such as their accessible surface area and mean hydration, is studied. The capacity of the polar atoms to form hydrogen bonds with water molecules and participate in protein–water networks are investigated. The locations of such networks are identified for both proteins. Proteins 2004. © 2004 Wiley‐Liss, Inc.
The molecular origin of the thiamin diphosphate‐induced spectral bands of ThDP‐dependent enzymes
Authors: Kovina Marina V. , de Kok Aart , Sevostyanova Irina A. , Khailova Ludmila S. , Belkina Natalya V. , Kochetov German A. 
Published: April 2004

AbstractNew and previously published data on a variety of ThDP‐dependent enzymes such as baker's yeast transketolase, yeast pyruvate decarboxylase and pyruvate dehydrogenase from pigeon breast muscle, bovine heart, bovine kidney, Neisseria meningitidis and E. coli show their spectral sensitivity to ThDP binding. Although ThDP‐induced spectral changes are different for different enzymes, their universal origin is suggested as being caused by the intrinsic absorption of the pyrimidine ring of ThDP, bound in different tautomeric forms with different enzymes. Non‐enzymatic models with pyrimidine‐like compounds indicate that the specific protein environment of the aminopyrimidine ring of ThDP determines its tautomeric form and therefore the changeable features of the inducible effect. A polar environment causes the prevalence of the aminopyrimidine tautomeric form (short wavelength region is affected). For stabilization of the iminopyrimidine tautomeric form (both short‐ and long‐wavelength regions are affected) two factors appear essential: (i) a nonpolar environment and (ii) a conservative carboxyl group of a specific glutamate residue interacting with the N1′ atom of the aminopyrimidine ring. The two types of optical effect depend in a different way upon the pH, in full accordance with the hypothesis tested. From these studies it is concluded that the inducible optical rotation results from interaction of the aminopyrimidine ring with its asymmetric environment and is defined by the protonation state of N1′ and the 4′‐nitrogen. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Alternative alignments from comparison of protein structures
Authors: Shih Edward S.C. , Hwang Ming‐Jing 
Published: April 2004

AbstractComparison of two protein structures often results in not only a global alignment but also a number of distinct local alignments; the latter, referred to as alternative alignments, are however usually ignored in existing protein structure comparison analyses. Here, we used a novel method of protein structure comparison to extensively identify and characterize the alternative alignments obtained for structure pairs of a fold classification database. We showed that all alternative alignments can be classified into one of just a few types, and with which illustrated the potential of using alternative alignments to identify recurring protein substructures, including the internal structural repeats of a protein. Furthermore, we showed that among the alternative alignments obtained, permuted alignments, which included both circular and scrambled permutations, are as prevalent as topological alignments. These results demonstrated that the so far largely unattended alternative alignments of protein structures have implications and applications for research of protein classification and evolution. Proteins 2004. © 2004 Wiley‐Liss, Inc.
NrdH‐redoxin of Corynebacterium ammoniagenes forms a domain‐swapped dimer
Authors: Stehr Matthias , Lindqvist Ylva 
Published: April 2004

AbstractNrdH‐redoxins constitute a family of small redox proteins, which contain a conserved CXXC sequence motif, and are characterized by a glutaredoxin‐like amino acid sequence but a thioredoxin‐like activity profile. Here we report the structure of Corynebacterium ammoniagenes NrdH at 2.7 Å resolution, determined by molecular replacement using E. coli NrdH as model. The structure is the first example of a domain‐swapped dimer from the thioredoxin family. The domain‐swapped structure is formed by an inter‐chain two‐stranded anti‐parallel β‐sheet and is stabilized by electrostatic interactions at the dimer interface. Size exclusion chromatography, and MALDI‐ESI experiments revealed however, that the protein exists as a monomer in solution. Similar to E. coli NrdH‐redoxin and thioredoxin, C. ammoniagenes NrdH‐redoxin has a wide hydrophobic pocket at the surface that could be involved in binding to thioredoxin reductase. However, the loop between α2 and β3, which is complementary to a crevice in the reductase in the thioredoxin–thioredoxin reductase complex, is the hinge for formation of the swapped dimer in C. ammoniagenes NrdH‐redoxin. C. ammoniagenes NrdH‐redoxin has the highly conserved sequence motif W61‐S‐G‐F‐R‐P‐[DE]67 which is unique to the NrdH‐redoxins and which determines the orientation of helix α3. An extended hydrogen‐bond network, similar to that in E. coli NrdH‐redoxin, determines the conformation of the loop formed by the conserved motif. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Density functional theory study on isomerization reactions of pyridazine derivatives bearing N,N‐dialkylaminoethyl group
Authors: Zhou Ziyan , Pan Xiumei , Wu Xue , Su Zhongmin , Kan Yuhe , Xie Yuzhong 
Published: April 2004

AbstractThe isomerization reactions of four pyridazine derivatives, i.e., 6‐chloro‐3‐hydroxy‐pyridazine, 1,2‐dihydrogen‐1‐methyl‐3,6‐pyridazindione, 6‐chloro‐3‐diethylamino‐ethoxy‐pyridazine, and 1‐methyl‐2‐diethylaminoethyl‐3,6(2H)‐pyridazindione, have been studied using density functional theory (DFT) B3LYP method at the 6‐311+G** basis set. The geometric structures of reactants, transition states and products have been optimized. The transition states have been explored and proved by vibration analysis as well as intrinsic reaction coordination (IRC) analysis. The activation energies of four reactions were calculated, and the corresponding isomerization mechanisms were also elucidated in theory. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Comparison of HF, HF + MP2, LDA, BLYP, and B3LYP band structures of the homopolypeptides
Authors: Ladik J. , Bogar F. , Penke B. 
Published: April 2004

AbstractAb initio HF, HF + MP2, LDA DFT, BLYP DFT, and B3LYP DFT calculations are compared in the case of 19 homopolypeptides in their β pleated sheet conformation. The results show that the B3LYP method provides good results for the fundamental gaps, as compared with the values estimated on the basis of available UV spectra and intermediate exciton calculations for PolyGly and PolyAla. The HF method gives the best agreement, using Koopman's theorem for the ionization potential, taking the calculated VBmax values in the HF case if one compares them with the experimental ionization potentials of the 19 amino acids measured by mass spectroscopy. Finally, how these methods might be improved to determine the most stable conformations of the homopolypeptides is outlined. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
A rapid and sensitive method for quantitation of nucleosides in human urine using liquid chromatography/mass spectrometry with direct urine injection
Authors: Lee Sang Hee , Jung Byung Hwa , Kim Sun Yeou , Chung Bong Chul 
Published: April 2004

AbstractOxidized nucleosides are biochemical markers for tumors, aging, and neurodegenerative diseases. However, during the last decade, the analytical methods for nucleosides by gas chromatography/mass spectrometry (GC/MS) and high‐performance liquid chromatography (HPLC) with single‐parameter detectors like electron‐capture detection (ECD) have not been sufficiently rapid or reliable to detect nucleosides in urine and to analyze clinical samples. It has been reported (Dudley et al., Rapid Commun Mass Spectrom. 2000; 14: 1200) that liquid chromatography with electrospray mass spectrometry (LC/ESI‐MS) is more specific and sensitive for analysis of nucleosides than HPLC with conventional detectors; however, this method required complex extraction steps. In the present work a direct LC/ESI‐MS method for nucleosides without extraction of urine samples has been developed. Analysis of nucleosides using positive‐ion mode with selected reaction monitoring effectively eliminated potential interferences from endogenous constituents of the urine. This highly selective and sensitive method made it possible to analyze urinary nucleosides with a lower limit of quantitation of 0.2 nmol/mL. The method has been validated, with both excellent linearity and reproducibility, in the calibration range from 0.2–400 nmol/mL. The correlation coefficients of the calibration curves were higher than 0.987. The coefficients of variation were in the range 0.03–14.92% (inter‐day) and 0.54–14.39% (intra‐day), respectively. Copyright © 2004 John Wiley & Sons, Ltd.
A mass spectrometric and molecular orbital study of H2O loss from protonated tryptophan and oxidized tryptophan derivatives
Authors: Lioe Hadi , O'Hair Richard A. J. , Reid Gavin E. 
Published: April 2004

AbstractProtonated N‐acetyltryptophan, oxindolylalanine (a mono‐oxidized derivative of tryptophan), and N‐acetyloxindolylalanine, as well as several di‐ and tripeptide derivatives containing oxindolylalanine, undergo a range of fragmentation reactions in the gas phase, including the loss of water. In order to elucidate the sites of water loss within these ions, and to determine the mechanisms associated with these processes, we have conducted a series of experiments employing multistage tandem mass spectrometry (MS/MS and MS3) in a quadrupole ion trap mass spectrometer, regiospecific structural labeling, and independent solution‐phase syntheses of proposed product ion structures, coupled with the use of molecular orbital calculations at the B3LYP/6‐31G* level of theory. We demonstrate that the loss of H2O from the amide carbonyl group of protonated N‐acetyltryptophan O‐methyl ester occurs via a ‘side‐chain–backbone' neighboring group reaction to yield a protonated carboline derivative. In contrast, the loss of water from the O‐methyl ester of protonated oxindolylalanine results in the formation of a tricyclic structure by ‘backbone–side‐chain’ nucleophilic attack from the amino nitrogen to the C2 position of the indole ring. The O‐methyl ester of protonated N‐acetyloxindolylalanine was found to dissociate via the loss of water from both possible sites, i.e. from the side‐chain indolyl oxygen and the backbone amide carbonyl group. An estimate of the relative preference for water loss from each site was obtained from the abundances of product ions formed from MS3 analysis of regiospecifically labeled derivatives of N‐acetyloxindolylalanine, and from the results of molecular orbital calculations. These studies indicate the absence of a characteristic ‘signature’ ion or neutral loss for peptides containing oxindolylalanine residues under low‐energy ion trap CID conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of mutated transporters associated with antigen‐processing 2 on characteristic major histocompatibility complex binding peptides: analysis using electrospray ionization tandem mass spectrometry
Authors: Kageyama G. , Kawano S. , Kanagawa S. , Kondo S. , Sugita M. , Nakanishi T. , Shimizu A. , Kumagai S. 
Published: April 2004

AbstractA novel allele of transporters associated with the antigen‐processing (TAP) 2 gene, TAP2*Bky2 (Val577), is significantly increased in Japanese patients with Sjögren's syndrome (SS), and has a strong association with SS‐A/Ro autoantibody production in SS and autoantibody including anti‐SS‐A/Ro and anti‐U1 RNP antibody in systemic lupus erythematosus (SLE). To determine the influence of this natural mutated TAP on peptides loaded onto MHC class I, we analyzed the repertoire of peptides loaded onto MHC class I on transfectants with TAP1 and TAP2 or mutated TAP2 by electrospray ionization tandem mass spectrometry (ESI‐MS/MS). After comparison of the peptide profiles we identified three peptides from only mutated TAP transfectants. Moreover, one of these peptides is derived from snRNP A, which is a target for anti‐U1 RNP antibody. To our knowledge this is the first report to show that the natural mutation of TAP2 changes the peptide profile loaded onto MHC class I molecules. Copyright © 2004 John Wiley & Sons, Ltd.
SPARE Parts: a C++ toolkit for string pattern recognition
Authors: Watson Bruce W. , Cleophas Loek 
Published: April 2004

AbstractIn this paper, we consider the design and implementation of SPARE Parts, a C++ toolkit for pattern matching. SPARE Parts (in particular, the 2003 version presented in this article) is the second generation string pattern matching toolkit by the authors. The toolkit, the first generic program for keyword pattern matching, contains implementations of the well‐known Knuth–Morris–Pratt, Boyer–Moore, Aho–Corasick and Commentz–Walter algorithms (and their variants).The toolkit is freely available for non‐commercial use. Copyright © 2004 John Wiley & Sons, Ltd.