bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of spread of adenocarcinoma in the prostate as related to cancer volume
Authors: McNeal John E. , Haillot Olivier 
Published: August 2002

AbstractBACKGROUNDPeripheral zone (PZ) and transition zone (TZ) cancers of the prostate remain confined to their zone of origin under 4 cc volume, with progressive molding to TZ boundary. In PZ cancer, growth in perineural spaces over 4 cc volume directs cancer toward the base, around subcapsular nerve trunks, and often transcapsular. This tendency to stereotyped patterns of cancer spread in the prostate is investigated systematically here for the first time.METHODSCancers in 571 radical prostatectomy specimens were sorted by zone of origin and tumor volume. A traced map of each cancer at 3 mm transverse intervals was assessed for location, contour, selected linear measures and the “transverse (largest) reference plane”.RESULTSSpread along prostate capsule characterized all but the smallest PZ cancers and was most extensive transversely. By 4 cc volume, most PZ cancers' transverse reference plane filled one side of PZ. Above 4 cc, bilateral spread, TZ invasion, and nodularity progressively increased, but dominant growth was toward the base along nerves to the superior pedicle; here capsule penetration was most common. TZ cancers arose mainly in anterior‐mid TZ, invading anterior fibromuscular stroma (AFM) while small. AFM was massively invaded in many large tumors. Larger TZ cancers (> 4 cc) invaded anterolateral PZ but seldom penetrated posterior PZ.CONCLUSIONSPatterns and extent of spread of carcinoma in the prostate are stereotyped following a few principles regarding stromal interactions. Using these, sequential maps were presented of evolving prostate cancer contours at consecutive increasing volumes. Prostate 49:48–57, 2001. © 2001 Wiley‐Liss, Inc.
Crystal structure of Yeco from Haemophilus influenzae (HI0319) reveals a methyltransferase fold and a bound S‐adenosylhomocysteine
Authors: Lim Kap , Zhang Hong , Tempczyk Aleksandra , Bonander Nicklas , Toedt John , Howard Andrew , Eisenstein Edward , Herzberg Osnat 
Published: August 2002

AbstractThe crystal structure of YecO from Haemophilus influenzae (HI0319), a protein annotated in the sequence databases as hypothetical, and that has not been assigned a function, has been determined at 2.2‐Å resolution. The structure reveals a fold typical of S‐adenosyl‐L‐methionine‐dependent (AdoMet) methyltransferase enzymes. Moreover, a processed cofactor, S‐adenosyl‐L‐homocysteine (AdoHcy), is bound to the enzyme, further confirming the biochemical function of HI0319 and its sequence family members. An active site arginine, shielded from bulk solvent, interacts with an anion, possibly a chloride ion, which in turn interacts with the sulfur atom of AdoHcy. The AdoHcy and nearby protein residues delineate a small solvent‐excluded substrate binding cavity of 162 Å3 in volume. The environment surrounding the cavity indicates that the substrate molecule contains a hydrophobic moiety and an anionic group. Many of the residues that define the cavity are invariant in the HI0319 sequence family but are not conserved in other methyltransferases. Therefore, the substrate specificity of YecO enzymes is unique and differs from the substrate specificity of all other methyltransferases sequenced to date. Examination of the Enzyme Commission list of methyltransferases prompted a manual inspection of 10 possible substrates using computer graphics and suggested that the ortho‐substituted benzoic acids fit best in the active site. Proteins 2001;45:397–407. © 2001 Wiley‐Liss, Inc.
Hierarchy of simulation models in predicting molecular recognition mechanisms from the binding energy landscapes: Structural analysis of the peptide complexes with SH2 domains
Authors: Verkhivker Gennady M. , Bouzida Djamal , Gehlhaar Daniel K. , Rejto Paul A. , Schaffer Lana , Arthurs Sandra , Colson Anthony B. , Freer Stephan T. , Larson Veda , Luty Brock A. , Marrone Tami , Rose Peter W. 
Published: August 2002

AbstractComputer simulations using the simplified energy function and simulated tempering dynamics have accurately determined the native structure of the pYVPML, SVLpYTAVQPNE, and SPGEpYVNIEF peptides in the complexes with SH2 domains. Structural and equilibrium aspects of the peptide binding with SH2 domains have been studied by generating temperature‐dependent binding free energy landscapes. Once some native peptide–SH2 domain contacts are constrained, the underlying binding free energy profile has the funnel‐like shape that leads to a rapid and consistent acquisition of the native structure. The dominant native topology of the peptide–SH2 domain complexes represents an extended peptide conformation with strong specific interactions in the phosphotyrosine pocket and hydrophobic interactions of the peptide residues C‐terminal to the pTyr group. The topological features of the peptide–protein interface are primarily determined by the thermodynamically stable phosphotyrosyl group. A diversity of structurally different binding orientations has been observed for the amino‐terminal residues to the phosphotyrosine. The dominant native topology for the peptide residues carboxy‐terminal to the phosphotyrosine is tolerant to flexibility in this region of the peptide–SH2 domain interface observed in equilibrium simulations. The energy landscape analysis has revealed a broad, entropically favorable topology of the native binding mode for the bound peptides, which is robust to structural perturbations. This could provide an additional positive mechanism underlying tolerance of the SH2 domains to hydrophobic conservative substitutions in the peptide specificity region. Proteins 2001;45:456–470. © 2001 Wiley‐Liss, Inc.
Identification of a novel class in the α/β hydrolase fold superfamily: The N‐myc differentiation‐related proteins
Authors: Shaw Eudean , McCue Lee Ann , Lawrence Charles E. , Dordick Jonathan S. 
Published: August 2002

AbstractThe α/β hydrolases constitute a large protein superfamily that mainly consists of enzymes that catalyze a diverse range of reactions. These proteins exhibit the α/β hydrolase fold, the essential features of which have recently been delineated: the presence of at least five parallel β‐strands, a catalytic triad in a specific order (nucleophile‐acid‐histidine), and a nucleophilic elbow. Because of the difficulties experimentally in identifying protein structures, we have used a Bayesian computational algorithm (PROBE) to identify the members of this superfamily based on distant sequence relationships. We found that the presence of five sequence motifs, which contain residues important for substrate binding and stabilization of the fold, are required for membership in this superfamily. The superfamily consists of at least 909 members, including the N‐myc downstream regulated proteins, which are believed to be involved in cell differentiation. Unlike most of the other superfamily members, the N‐myc downstream regulated proteins have never been proposed to possess the α/β hydrolase fold and do not appear to be hydrolases. Proteins 2002;47:163–168. © 2002 Wiley‐Liss, Inc.
The nature of intermolecular interactions between aromatic amino acid residues
Authors: Gervasio Francesco Luigi , Chelli Riccardo , Procacci Piero , Schettino Vincenzo 
Published: August 2002

AbstractThe nature of intermolecular interactions between aromatic amino acid residues has been investigated by a combination of molecular dynamics and ab initio methods. The potential energy surface of various interacting pairs, including tryptophan, phenilalanine, and tyrosine, was scanned for determining all the relevant local minima by a combined molecular dynamics and conjugate gradient methodology with the AMBER force field. For each of these minima, single‐point correlated ab initio calculations of the binding energy were performed. The agreement between empirical force field and ab initio binding energies of the minimum energy structures is excellent. Aromatic–aromatic interactions can be rationalized on the basis of electrostatic and van der Waals interactions, whereas charge transfer or polarization phenomena are small for all intermolecular complexes and, particularly, for stacked structures. Proteins 2002;48:117–125. © 2002 Wiley‐Liss, Inc.
Crystal structures of the peanut lectin–lactose complex at acidic pH: Retention of unusual quaternary structure, empty and carbohydrate bound combining sites, molecular mimicry and crystal packing directed by interactions at the combining site
Authors: Ravishankar R. , Thomas C.J. , Suguna K. , Surolia A. , Vijayan M. 
Published: August 2002

AbstractThe crystal structures of a monoclinic and a triclinic form of the peanut lectin–lactose complex, grown at pH 4.6, have been determined. They contain two and one crystallographically independent tetramers, respectively. The unusual “open” quaternary structure of the lectin, observed in the orthorhombic complex grown in neutral pH, is retained at the acidic pH. The sugar molecule is bound to three of the eight subunits in the monoclinic crystals, whereas the combining sites in four are empty. The lectin–sugar interactions are almost the same at neutral and acidic pH. A comparison of the sugar‐bound and free subunits indicates that the geometry of the combining site is relatively unaffected by ligand binding. The combining site of the eighth subunit in the monoclinic crystals is bound to a peptide stretch in a loop from a neighboring molecule. The same interaction exists in two subunits of the triclinic crystals, whereas density corresponding to sugar exists in the combining sites of the other two subunits. Solution studies show that oligopeptides with sequences corresponding to that in the loop bind to the lectin at acidic pH, but only with reduced affinity at neutral pH. The reverse is the case with the binding of lactose to the lectin. A comparison of the neutral and acidic pH crystal structures indicates that the molecular packing in the latter is directed to a substantial extent by the increased affinity of the peptide loop to the combining site at acidic pH. Proteins 2001;43:260–270. © 2001 Wiley‐Liss, Inc.
Allosteric free energy changes at the α1β2 interface of human hemoglobin probed by proton exchange of Trpβ37
Authors: Mihailescu Mihaela‐Rita , Fronticelli Clara , Russu Irina M. 
Published: August 2002

AbstractThe energetic changes that occur on ligand binding in human hemoglobin have been investigated by measurements of the exchange rates of the indole proton of Trpβ37(C3). The Trpβ37 residues are located in helices C of the β‐subunits and are involved in contacts with the segments FG of the α‐subunits at the interdimeric α1β2 and α2β1 interfaces of the hemoglobin tetramer. In the quaternary structure change that accompanies ligand binding to hemoglobin, these contacts undergo minimal changes in relative orientation and in packing, thereby acting as hinges, or flexible joints. The exchange rates of the indole proton of Trpβ37(C3) were measured by nuclear magnetic resonance spectroscopy, in both deoxygenated and ligated hemoglobin. The results indicate that, at 15°C, the exchange rate is increased from 9.0 · 10−6 to 3.3 · 10−4 s−1 upon ligand binding to hemoglobin. This change suggests that the structural units at the hinge regions of the α1β2/α2β1 interfaces containing Trpβ37(C3) are specifically stabilized in unligated hemoglobin, and experience a change in structural free energy of ∼4 kcal/(mol tetramer) upon ligand binding. Therefore, the hinge regions of the α1β2/α2β1 interfaces could play a role in the transmission of free energy through the hemoglobin molecule during its allosteric transition. Proteins 2001;44:73–78. © 2001 Wiley‐Liss, Inc.
Binding of AMP to two of the four subunits of pig kidney fructose‐1,6‐bisphosphatase induces the allosteric transition
Authors: Kelley‐Loughnane Nancy , Kantrowitz Evan R. 
Published: August 2002

AbstractTo study the allosteric transition in pig kidney fructose 1,6‐bisphosphatase (FBPase), we constructed hybrids in which subunits have either their active or regulatory sites rendered nonfunctional by specific mutations. This was accomplished by the coexpression of the enzyme from a plasmid that contained two slightly different copies of the cDNA. To resolve and purify each of the hybrid enzymes, six aspartic acid codons were added before the termination codon of one of the cDNAs. The addition of these Asp residues to the protein did not alter the kinetic or allosteric properties of the resulting FBPase. Expression of the enzyme from a dual‐gene plasmid resulted in the production of a set of five different enzymes (two homotetramers and three hybrid tetramers) that could be purified by a combination of affinity and anion‐exchange chromatography because of the differential charge on each of these species. The hybrid with one subunit that only had a functional regulatory site (R) and three subunits that only had a functional active site (A) exhibited biphasic AMP inhibition. Analysis of these data suggest that the binding of AMP to the R subunit is able to globally alter the activity of the other three A subunits. The hybrid composed of two R and two A subunits is completely inhibited at an AMP concentration of ≈0.5 mM, 100‐fold less than the concentration required to fully inhibit the A4 enzyme. The monophasic nature of this cooperative inhibition suggests that the AMP binding to the two R subunits is sufficient to completely inhibit the enzyme and suggests that the binding of AMP to only two of the four subunits of the enzyme induces the global allosteric transition from the R to the T state. Proteins 2001;44:255–261. © 2001 Wiley‐Liss, Inc.
α‐Helix formation: Discontinuous molecular dynamics on an intermediate‐resolution protein model
Authors: Voegler Smith Anne , Hall Carol K. 
Published: August 2002

AbstractAn intermediate‐resolution model of small, homogeneous peptides is introduced, and discontinuous molecular dynamics simulation is applied to study secondary structure formation. Physically, each model residue consists of a detailed three‐bead backbone and a simplified single‐bead side‐chain. Excluded volume and hydrogen bond interactions are constructed with discontinuous (i.e., hard‐sphere and square‐well) potentials. Simulation results show that the backbone motion of the model is limited to realistic regions of Φ–Ψ conformational space. Model polyalanine chains undergo a locally cooperative transition to form α‐helices that are stabilized by backbone hydrogen bonding, while model polyglycine chains tend to adopt nonhelical structures. When side‐chain size is increased beyond a critical diameter, steric interactions prevent formation of long α‐helices. These trends in helicity as a function of residue type have been well documented by experimental, theoretical, and simulation studies and demonstrate the ability of the intermediate‐resolution model developed in this work to accurately mimic realistic peptide behavior. The efficient algorithm used permits observation of the complete helix–coil transition within 15 min on a single‐processor workstation, suggesting that simulations of very long times are possible with this model. Proteins 2001;44:344–360. © 2001 Wiley‐Liss, Inc.
Computational 3‐D modeling and site‐directed mutation of an antibody that binds Neu2en5Ac, a transition state analogue of a sialic acid
Authors: Kamei Hiroya , Shimazaki Kazuko , Nishi Yoshisuke 
Published: August 2002

AbstractAn antibody against a transition state analog (TSA) may share some common features with an enzyme that produces such a transition state. SIC172 antibody binds specifically to Neu2en5Ac, a TSA of Neu5Ac in the sialidase reaction, but has no catalytic activity. To understand how the antibody recognizes Neu2en5Ac and to find out if it is possible to convert it to a catalytic antibody, we made and sequenced the SIC172 ScFv, and constructed a 3‐D model of it. The VH‐CDR3 contains a unique sequence with Cys at H95. The 3‐D model showed that Cys‐H95 is exposed inside the antigen‐binding cavity. After affinity docking, 4 types emerged. In type I, the carboxyl group of Neu2en5Ac is located near the Cys‐H95 and neighboring positively charged residues. The change of Cys‐H95 to Asp by site‐directed mutation decreased the binding activity, while a change to Arg did not. These and other mutation experiments, and further modeling of mutant Fv, support the 3‐D model and docking type I. A comparison with sialidase indicates that SIC172 antibody appears to have some groups of residues that are conserved at the active site of the enzyme. The possibility of Neu2en5Ac‐binding antibody being converted to a catalytic antibody is discussed. Proteins 2001;45:285–296. © 2001 Wiley‐Liss, Inc.
Phylogenetic information improves homology detection
Authors: Rehmsmeier Marc , Vingron Martin 
Published: August 2002

AbstractWe present a database search method that is based on phylogenetic trees (treesearch). The method is used to search a protein sequence database for homologs to a protein family. In preparation for the search, a phylogenetic tree is constructed from a given multiple alignment of the family. During the search, each database sequence is temporarily inserted into the tree, thus adding a new edge to the tree. Homology between family and sequence is then judged from the length of this edge. In a comparison of our method to profiles (ISREC pfsearch), two implementations of hidden Markov models (HMMER hmmsearch and SAM hmmscore), and to the family pairwise search (FPS) method on 43 families from the SCOP database based on minimum false‐positive counts (min‐FPCs), we found a considerable gain in sensitivity. In 69% of the test cases, treesearch showed a min‐FPC of at most 50, whereas the two second best methods (hmmsearch and FPS) showed this performance only in 53% cases. A similar impression holds for a large range of min‐FPC thresholds. The results demonstrate that phylogenetic information can significantly improve the detection of distant homologies and justify our method as a useful alternative to existing methods. Proteins 2001;45:360–371. © 2001 Wiley‐Liss, Inc.
Entropy calculations on the molten globule state of a protein: Side‐chain entropies of α‐lactalbumin
Authors: Schäfer Heiko , Smith Lorna J. , Mark Alan E. , van Gunsteren Wilfred F. 
Published: August 2002

AbstractWe present entropy estimates based on molecular dynamics simulations of models of the molten globule state of the protein α‐lactalbumin at low pH. The entropy calculations use the covariance matrix of atom‐positional fluctuations and yield the complete configurational entropy. The configurational entropy of the entire protein and of each of its side chains is calculated. Exposed side chains show a larger entropy compared to buried side chains. A comparison to data from rotamer counting is made and significant differences are found. Proteins 2002;46:215–224. © 2001 Wiley‐Liss, Inc.
Mode of action of the ecdysone agonist tebufenozide (RH‐5992), and an exclusion mechanism to explain resistance to it
Authors: Retnakaran Arthur , Gelbic Ivan , Sundaram Meenakshi , Tomkins William , Ladd Tim , Primavera Mark , Feng Qili , Arif Basil , Palli Reddy , Krell Peter 
Published: August 2002

AbstractSpruce budworm larvae (Choristoneura fumiferana) upon ingesting tebufenozide (RH‐5992) stop feeding and go into a precocious, incomplete molt, leading eventually to death. Like 20‐hydroxyecdysone (20E), tebufenozide also acts at the receptor level and transactivates the expression of up‐regulated genes but, because of its persistence, the down‐regulated genes that are normally expressed in the absence of 20E are not expressed. While tebufenozide is lepidopteran‐specific, an analog, RH‐5849, is effective on dipterans. This is reflected in the respective effects of the two compounds on Cf‐203 (C. fumiferana ‐ 203), a lepidopteran cell line and Dm‐2 (Drosophila melanogaster ‐ 2), a dipteran cell line. Cf‐203 cells accumulated [14C]tebufenozide and expressed CHR3 (Choristoneura hormone receptor 3), but Dm‐2 cells excluded the material and did not express DHR3 (Drosophila hormone receptor 3). Using yeast ABC (ATP binding cassette) transporter mutants, we determined that PDR5 (pleiotropic drug resistance 5) was responsible for the exclusion. We discovered recently that older instars of the white‐marked tussock moth (Orgyia leucostigma) are resistant to tebufenozide, perhaps as a result of such an exclusion system. We are currently cloning PDR5 (pleiotropic drug resistance 5), which is an essential step in studying the resistance mechanism.© 2001 Society of Chemical Industry
Identification of alternatives for the management of foliar nematodes in floriculture
Authors: Jagdale Ganpati B , Grewal Parwinder S 
Published: August 2002

AbstractThe foliar nematodes, Aphelenchoides spp, have emerged as important pests of ornamentals in North America during the last decade. Due to the ban on the use of potentially toxic pesticides, there are currently no nematicides registered to manage foliar nematodes on ornamentals. Therefore, we have evaluated a biological [Burkholderia cepacia (syn Pseudomonas cepacia)], two plant products [clove (Syzygium aromaticum) extract and Nimbecidine (azadirachtin)] and twelve chemical pesticides registered for the management of insects, mites, slugs or diseases of ornamentals, against Aphelenchoides fragariae on the most popular ornamental, hosta (Hosta spp), for two consecutive years. We found ZeroTol (270 g liter−1 peroxyacetic acid), currently labeled as a broad‐spectrum fungicide/algicide, to be a very potent nematicide that killed 100% of the nematodes in water suspension. It also caused over 70% reduction in A fragariae population in soil and in the leaves without any phytotoxicity. B cepacia caused 67–85% reduction in A fragariae population in leaves and 50% reduction in the soil whereas insecticidal soap caused over 72% reduction in leaves and 61% reduction in the soil. Clove extract and Nimbecidine did not show any potential for the control of A fragariae on hosta. Although all twelve chemical pesticides were effective in reducing the population of A fragariae in the soil 45 days after treatment (DAT), only diazinon 475 g liter−1 EC, trichlorfon 800 g kg−1 SP, ethoprophos 100 g kg−1 GR, oxamyl 100 g kg−1 GR and ZeroTol caused over 70% reduction in nematode population compared with the control. In the leaves, only diazinon EC, trichlorfon SP, insecticidal soap, oxamyl GR and ZeroTol consistently caused over 70% nematode population reduction compared with the control at 45 DAT in both years. Thus, only diazinon EC, trichlorfon SP, oxamyl GR and ZeroTol consistently caused over 70% reduction in nematode population both in soil and leaves. Due to the recent ban by the US Environmental Protection Agency on the use of the first three of these formulations, only ZeroTol would serve as an effective tool to manage foliar nematodes in ornamentals. Although not as effective as ZeroTol in the soil, insecticidal soap is the only other alternative for foliar nematode management.© 2002 Society of Chemical Industry