bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting molecular interactions and inducible complementarity: Fragment docking of fab‐peptide complexes
Authors: Friedman Alan R. , Roberts Victoria A. , Tainer John A. 
Published: May 2005

AbstractAntibody‐antigen interactions are representative of a broad class of receptor‐ligand interactions involving both specificity and potential inducible complementarity. To test possible mechanisms of antigenantibody recognition and specificity computationally, we have used a Metropolis Monte Carlo algorithm to dock fragments of the epitope Glu‐Val‐Val‐Pro‐His‐Lys‐Lys to the X‐ray structures of both the free and the complexed Fab of the antibody B13I2 (raised against the C‐helix of myohemerythri). The fragments Pro‐His and Val‐Pro‐His, which contain residues experimentally identified as important for binding, docked correctly to both structures, but all tetrapeptide and larger fragments docked correctly only to the complexed Fab, even when torsional flexibility was added to the ligand. However, only tetrapeptide and larger fragments showed significantly more favorable energies when docked to the complexed Fab coordinates than when docked to either the free Fab or a non‐specific site remote from the combining site. Comparison of the free and complexed B13I2 structures revealed that atoms within 5 Å of Val‐Pro‐His showed little movement upon peptide binding, but atoms within 5 Å of the other four epitope residues showed greater movements. These results computationally distinguish recognition and binding processes with practical implications for drug design strategies. Overall, this new fragment docking approach establishes distinct roles for the “lock‐and‐key” (recognition) and the “handshake” (binding) paradigms in antibody‐antigen interaction, suggests an incremental approach to incorporating flexibility in computational docking, and identifies critical regions within receptor binding sites for ligand recognition. © 1994 Wiley‐Liss, Inc.
Cold adaption of enzymes: Structural comparison between salmon and bovine trypsins
Authors: Smalås Arne O. , Heimstad Eldbjørg S. , Hordvik Asbjørn , Willassen Nils P. , Male Rune 
Published: May 2005

AbstractThe crystal structure of an anionic form of salmon trypsin has been determined at 1.82 Å resolution. We report the first structure of a trypsin from a phoikilothermic organism in a detailed comparison to mammalian trypsins in order to look for structural rationalizations for the cold‐adaption features of salmon trypsin. This form of salmon trypsin (T II) comprises 222 residues, and is homologous to bovine trypsin (BT) in about 65% of the primary structure. The tertiary structures are similar, with an overall displacement in main chain atomic positions between salmon trypsin and various crystal structures of bovine trypsin of about 0.8 Å. Intramolecular hydrogen bonds and hydrophobic interactions are compared and discussed in order to estimate possible differences in molecular flexibility which might explain the higher catalytic efficiency and lower thermostability of salmon trypsin compared to bovine trypsin. No overall differences in intramolecular interactions are detected between the two structures, but there are differences in certain regions of the structures which may explain some of the observed differences in physical properties. The distribution of charged residues is different in the two trypsins, and the impact this might have on substrate affinity has been discussed. © 1994 Wiley‐Liss, Inc.
Crystallization and characterization of the recombinant human Clara cell 10‐kDa protein
Authors: Matthews John H. , Pattabiraman N. , Ward Keith B. , Mantile Giuditta , Miele Lucio , Mukherjee Anil B. 
Published: May 2005

AbstractCrystals of recombinant human Clara cell 10‐kDa protein were grown both from ammonium sulfate and polyethylene glycol (PEG) solutions. Crystals grown from ammonium sulfate solution have been characterized by X‐ray diffraction studies as monoclinic with the space group C2 and lattice constants a = 69.2 Å, b = 83.0 Å, c = 58.3 Å, and β = 99.7°. The monoclinic crystals diffract to beyond 2.5 Å. Some of the crystals grown from PEG were of a similar habit to those grown from ammonium sulfate, but others were triclinic with the space group P1 and cell constants a = 40.3 Å, b = 46.3 Å, c = 51.3 Å, α = 117.7°, β = 102.3°, and γ = 71.4°. These crystals diffract to beyond 3.2 Å. © 1994 Wiley‐Liss, Inc.
Crystallization of the reaction center from Rhodobacter sphaeroides in a new tetragonal form
Authors: Allen J. P. 
Published: May 2005

AbstractThe reaction center from the nonsulfur purple bacteriumRhodobacter sphaeroideshas been crystallized in a new form. The crystals grew in the presence of polyethylene glycol 4000, the detergent β‐octyl glucoside, and the amphiphiles heptane triol and benzamidine hydrochloride, using the sitting drop method. The space group of these crystals is tetragonal, P41(43)212, and the cell constants are a = b = 141.5 Å and c = 276.7 Å with probably 2 proteins per asymmetric unit. A native data set has been set collected to a resolution of 2.8 Å consisting of 56,332 unique reflections (50,731 with F > 2σ) with anRsym of 9.5%. Analysis of the diffraction data is underway using molecular and isomorphous replacement. © 1994 Wiley‐Liss, Inc.
A model for the structure of a homodimeric prohormone: The precursor to the locust neuropeptide AKH I
Authors: Horne T. J. , Doak D. G. , Rayne R. C. , Balacco G. , O'Shea M. , Campbell I. D. 
Published: May 2005

AbstractWe have determined the structure in solution of a homodimeric protein that is a precursor to the locust neuropeptide adipokinetic hormone I using nuclear magnetic resonance spectroscopy. This precursor, called P1, is comprised of two 41 residue strands joined by a single inter‐chain disulphide at Cys39. We have also determined the structure of an end product of P1 processing, called APRP1; this is a homodimer comprised of residues 14–41 of PI. Nuclear Overhauser Effect (nOe) data indicate that in both P1 and APRP1, residues 22–37 (numbered with respect to P1) form pairs of α‐helices, with no evidence for any other secondary structure. © 1994 Wiley‐Liss, Inc.
Quantum mechanical model assembly study on the energetics of binding of arabinose, fucose, and galactose to L‐arabinose‐binding protein
Authors: Peräkylä Mikael , Pakkanen Tapani A. 
Published: May 2005

AbstractBinding energies ofL‐arabinose, D‐fucose, and D‐galactose to L‐arabinose‐binding protein was investigated theoretically. The calculated binding energies were composed of three contributions: (1) direct ligand‐active site interaction energies calculated using static ab initio model assemblies; (2) solvation energies of the ligands; and (3) long‐range electrostatic interaction energies between the ligands and the protein matrix. The calculated binding energies and the contributions of the energy components were used to analyze the experimental affinities of the ligands. © 1994 Wiley‐Liss, Inc.
Predicted secondary and supersecondary structure for the serine–threonine‐specific protein phosphatase family
Authors: Jenny Thomas F. , Gerloff Dietlind L. , Cohen Mark A. , Benner Steven A. 
Published: May 2005

AbstractA bona fide consensus prediction for the secondary and supersecondary structure of the serine–threonine specific protein phosphatases is presented. The prediction includes assignments of active site segments, an internal helix, and a region of possible 310 helical structure. An experimental structure for a member of this family of proteins should appear shortly, allowing this prediction to be evaluated. © 1995 Wiley‐Liss, Inc.
Model assembly study of the ligand binding by p‐hydroxybenzoate hydroxylase: Correlation between the calculated binding energies and the experimental dissociation constants
Authors: Peräkylä Mikael , Pakkanen Tapani A. 
Published: May 2005

AbstractThe energies of binding of seven ligands by p‐hydroxybenzoate hydroxylase (PHBH) were calculated theoretically. Direct enzyme–ligand interaction energies were calculated using the ab initio quantum mechanical model assembly of the active site at the 3‐21G level. Solvation energies of the ligands needed in the evaluation of the binding energies were calculated with the semiempirical AM1–SM2 method and the long‐range electrostatic interaction energies between the ligands and the protein matrix classically using the static charge distributions of the ligands and the protein. Energies for proton‐transfer between the ligands OH or SH substituent at position 4 and the active‐site tyrosine within the ab initio model assemblies were calculated and compared to the corresponding pKas in aqueous solution. Excluding 3,4‐dihydroxybenzoate, the natural product of PHBH, a linear relationship between the calculated binding energies and the experimental binding free energies was found with a correlation coefficient of 0.90. Contributions of the direct enzyme–ligand interaction energies, solvation energies and the long‐range electrostatic interaction energies to the calculated binding energies were analyzed. The proton‐transfer energies of the ligands with substituents ortho to the ionized OH were found to be perturbed less in the model calculations than the energies of their meta isomers as deduced from the corresponding pKas. © 1995 Wiley‐Liss, Inc.
Crystallization and preliminary structural studies of the ncd motor domain
Authors: Sablin Elena P. , Fletterick Robert J. 
Published: May 2005

AbstractThe motor domain of the kinesin homolog ncd has been crystallized in the presence of MgATP by the vapor diffusion method using polyethylene glycol as the precipitant. The crystals belong to the orthorhombic space group I222 with unit cell dimensions a = 127.1 Å, b = 122.3 Å, c = 68.0 Å, and there is one ncd molecule per asymmetric unit. The crystals diffract X‐ray to at least 2.3 Å and are appropriate for high‐resolution structure determination. © 1995 Wiley‐Liss, Inc.
Preliminary X‐ray diffraction analysis of crystals of turnip yellow mosaic virus (TYMV)
Authors: Canady Mary A. , Day John , McPherson Alexander 
Published: May 2005

AbstractTurnip yellow mosaic virus (TYMV) was purified from Chinese cabbage and crystallized in a form that permits high resolution structural analysis using X‐ray diffraction. The crystals have a hexagonal bipyramidal morphology and often achieve dimensions of 1.0 × 1.0 × 0.5 mm. The crystals appear to be of hexagonal space group P6222 with a = b = 525 Å, c=315 Å, but we cannot strictly rule out the possibility that the space group is P622. They appear different than any crystals of TYMV previously reported. There are three T = 3 virus particles in the unit cell, which implies that one quarter of the particle, or 45 protein subunits, comprises the asymmetric unit of the crystal. Native data have been collected using synchrotron radiation to a resolution of 3.2 Å. © 1995 Wiley‐Liss, Inc.
Configurational effects in antibody–antigen interactions studied by microcalorimetry
Authors: Murphy Kenneth P. , Freire Ernesto , Paterson Yvonne 
Published: May 2005

AbstractIn this paper we study the binding of two monoclonal antibodies, E3 and E8, to cytochrome c using high‐sensitivity isothermal titration calorimetry. We combine the calorimetric results with empirical calculations which relate changes in heat capacity to changes in entropy which arise from the hydrophobic effect. The change in heat capacity for binding E3 is −350 ± 60 cal K−1 mol−1 while for E8 it is −165 ± 40 cal K−1 mol−1. This result indicates that the hydrophobic effect makes a much larger contribution for E3 than for E8. Since the total entropy change at 25°C is very similar for both antibodies, it follows that the configurational entropy cost for binding E3 is much larger than for binding E8 (−77 ± 15 vs. −34 ± 11 cal K−1 mol−1). These results illustrate a case of entropy compensation in which the cost of restricting conformational degrees of freedom is to a large extent compensated by solvent release. We also show that the thermodynamic data can be used to make estimates of the surface area changes that occur upon binding. The results of the present study are consistent with previous hydrogen–deuterium exchange data, detected using 2D NMR, on the two antibody–antigen interactions. The NMR study indicated that protection from exchange is limited to the binding epitope for E8, but extends beyond the epitope for E3. These results were interpreted as suggesting that a larger surface area was buried on cytochrome c upon binding to E3 than to E8, and that larger changes in configurational entropy occur upon binding of E3 than E8. These findings are confirmed by the present study using isothermal titration calorimetry. © 1995 Wiley‐Liss, Inc.
Affinities of phosphorylated substrates for the E. coli tryptophan synthase α‐subunit: Roles of Ser‐235 and helix‐8′ dipole
Authors: Sarker Krishna D. , Hardman John K. 
Published: May 2005

AbstractThe roles of Ser‐235 and helix‐8′ (residues 235–242) in the functional binding and turnover of phosphorylated substrates by the α‐subunit of the E. coli tryptophan synthase (TSase) α2β2‐holoenzyme complex are examined. Previous crystallographic analyses indicated that this region was one of several near the phosphate moiety of the physiological substrate, indole‐3‐glycerol phosphate (IGP). The peptidyl amido group of Ser‐235 was suggested to H‐bond to the phosphate group; a helix macrodipole binding role was suggested for helix‐8′. The activities and substrate Kms of mutant α‐subunits altered in this region by site‐specific mutagenesis are reported here. Substitutions at Ser‐235 by an acidic (glutamic acid, mutant SE235), basic (lysine, mutant SK235), or a nonpeptidyl amido‐containing residue (proline, mutant SP235) exhibit 40‐ to 180‐fold Km increases for IGP and D‐glyceraldehyde‐3‐phosphate; no Km defects for indole were observed. kcat values for SP235, SE235, and SK235 are 100, 70, and 40%, respectively, of the wild‐type value. Steric considerations may explain the results with the SE235 and SK235 mutant α‐subunits; however, the SP235 results are consistent with the suggested phosphate binding role for the Ser‐235 peptidyl amide group during catalysis. A helix‐8′ dipole role was explored following proline substitutions separately at the first six (of eight) residues. Proline substitutions at positions‐1 through ‐4 in helix‐8′ have normal indole Kms and catalytic activities in all four TSase reactions, suggesting no major global structural changes in these proteins. By these criteria, substitutions at positions‐5 and ‐6 lead to significant structural alterations. Km increases for phosphorylated substrates are substantial (up to 40‐fold) and are dependent upon the presence of L‐serine at the β‐subunit active site. In the absence of L‐serine, substitution only at the first position results in binding defects; in the presence of L‐serine, substitutions at the first, second and third positions show binding defects of decreasing magnitude, sequentially. Substitutions at the fourth and fifth position have no effect on substrate binding. It is suggested that during catalysis a helix dipole effect on binding may be exerted but only via inter‐subunit‐induced conformational changes due to ligand (L‐serine) binding to the β‐subunit. © 1995 Wiley‐Liss, Inc.
Empirical evaluation of the influence of side chains on the conformational entropy of the polypeptide backbone
Authors: Stites Wesley E. , Pranata Julianto 
Published: May 2005

AbstractChanges in amino acid side chains have long been recognized to alterthe range and distribution of ϕ, ψ angles found in the main chain of polypeptides. Altering the range and distribution of ϕ, ψ angles also alters the conformational entropy of the flexible denatured state and may thus stabilize or destabilize it relative to the comparatively conformationally rigid native state. A database of 12,320 residues from 61 nonhomologous, high resolution crystal structures was examined to determine the ϕ, ψ conformational preferences of each of the 20 amino acids. These observed distributions in the native state of proteins are assumed to also reflect the distributions found in the denatured state. The distributionswere used to approximate the energy surface for each residue, allowing the calculation of relative conformational entropies for each residue relative to glycine. In the most extreme case, replacement of glycine by proline, conformational entropy changes will stabilize the native state relative to the denatured state by −0.82 ± 0.08 kcal/mol at 20°C. Surprisingly, alanine is found to be the most ordered residue other than proline. This unexpected result is a result of the high percentage of alanines found in helical conformations. This either indicates that the observed distributions in the native state do not reflect the distributions in the denatured state, or that alanine is much more likely to adopt a helical conformation in the denatured state than residues with longer side chains. Among those residues with ϕ, ψ angles compatible with helix incorporation the percentage of alanines actually in helices is very similar to other residues. This and the consistent ordering of alanine relative to other residues regardless of secondary structure are evidence that ϕ, ψ distributions in native states reflect those in the denatured states. © 1995 Wiley‐Liss, Inc.
Crystallization of UDP‐N‐acetylglucosamine O‐acyltransferase from Escherichia coli
Authors: Pfitzner Ute , Raetz Christian R. H , Roderick Steven L. 
Published: May 2005

AbstractCrystals of UDP‐N‐acetylglucosamine O‐acyltransferase (lpxA) fromEscherichia coli have been obtained from solutions of sodium/potassium phosphate and dimethylsulfoxide. These crystals belong to the cubic space group P213 (a = 99.0 Å), diffract X‐raysto approximately 2.5 Å resolution and contain one subunit of the enzyme in the asymmetric unit. © 1995 Wiley‐Liss, Inc.
Crystallization, characterization, and preliminary crystallographic studies of mitochondrial carbamoyl phosphate synthetase I ofRana catesbeiana
Authors: Marina Alberto , Bravo Jerónimo , Fita Ignacio , Rubio Vicente 
Published: May 2005

AbstractCarbamoyl phosphate synthetase I (ammonia; E C 6.3.4.16) was purified from the liver ofRana catesbeiana(bullfrog). Crystals of the protein have been obtained at 22°C by the hanging drop vapor diffusion technique, with polyethylene glycol as precipitant. Tetragonal crystals of about 0.3 × 0.3 × 0.7 mm diffract at room temperature to at least 3.5 Å using a conventional source and are stable to X‐radiation for about 12 h. Therefore, these crystals are suitablefor high resolution studies. The space group isP41212 (or its enantiomorphP43212), with unit cell dimensionsa=b= 291.6 Å andc= 189.4 Å. Density packing considerations areconsistent with the presence of 4‐6 monomers (Mrof the monomer, 160,000) in the asymmetric unit. Amino‐terminal sequence of the enzyme and of a chymotryptic fragment of 73.7 kDa containing the COOH‐terminus has been obtained. The extensive sequence identity with rat and human carbamoyl phosphate synthetase I indicates the relevance for mammals of structural data obtained with the frog enzyme. © 1995 Wiley‐Liss, Inc.
Hard α‐keratin IF: A structural model lacking a head‐to‐tail molecular overlap but having hybrid features characteristic of both epidermal keratin and vimentin IF
Authors: Parry David A. D. 
Published: May 2005

AbstractIn intermediate filaments (IF) both epidermal keratin and vimentin molecules have been shown to have an eight residue head to‐tail overlap between the rod domains of similarly directed molecules. In the case of the epidermal keratins this region has also been shown to have particular structural/functional significance since it represents a hot‐spot for mutations in the four keratinopathies characterized to date. While there is good evidence that this head‐to‐tail overlap is present in IF containing Type III, IV, and V chains, as well as in the epidermal keratin IF (Ib/IIb), there are no data currently available for the hard α‐keratin IF (Ia/IIa). Using a variety of data derived from X‐ray diffraction and crosslinking studies, as well as theoretical modeling, it is now possible to demonstrate that the overlap region is not a feature of hard α‐keratin IF. Indeed, it is shown that there is a nine residue gap between consecutive parallel molecules in the IF. An explanation for this observation is presented in terms of compensating disulfide bonds that occur both within the IF, and between the IF and the matrix in which the IF are embedded. © 1995 Wiley‐Liss, Inc.
Consensus preferred hydration sites in six FKBP12‐drug complexes
Authors: Faerman Carlos H. , Karplus P. Andrew 
Published: May 2005

AbstractA set of consens us hydration sites for the FK506‐FKBP12 complex are derived by comparing six FKBP12‐drug complexes. These hydration sites include a subset of the observed water molecules plus some sites that are occupied by neighboring protein atoms in the FK506‐FKBP12 crystal structure. Two hydration prediction algorithms, AUTO‐SOL and AQUARIUS2, showed significant increases in apparent efficacy using these consensus water sites, suggesting that our proposed set of consensus hydration sites is truly a better representation of the hydration properties of FKBP12 in solution. Predictably, the consensus hydration sites include all buried water molecules. Otherwise, the features of solvation sites included in the consensus list versus those discarded reveal no distinctive features that would allow them to be selected unambiguously without reference to multiple crystal forms. We suggest that analyses such as this one are a crucial prelude to any theoretical analysis aimed at understanding hydration properties. © 1995 Wiley‐Liss, Inc.
Zinc binding in proteins and solution: A simple but accurate nonbonded representation
Authors: Stote Roland H. , Karplus Martin 
Published: May 2005

AbstractForce field parameters that use a combination of Lennard‐Jones and electrostatic interactions are developed for divalent zinc and tested in solution and protein simulations. It is shown that the parameter set gives free energies of solution in good agreement with experiment. Molecular dynamics simulations of carboxypeptidase A and carbonic anhydrase are performed with these zinc parameters and the CHARMM 22 β all‐atom parameter set. The structural results are as accurate as those obtained in published simulations that use specifically bonded models for the zinc ion and the AMBER force field. The inclusion of longer‐range electrostatic interactions by use of the Extended Electrostatics model is found to improve the equilibrium conformation of the active site. It is concluded that the present parameter set, which permits different coordination geometries and ligand exchange for the zinc ion, can be employed effectively for both solution and protein simulations of zinc‐containing systems. © 1995 Wiley‐Liss, Inc.
Structure and internal dynamics of the bovine pancreatic trypsin inhibitor in aqueous solution from long‐time molecular dynamics simulations
Authors: Brunne R. M. , Berndt K. D. , Güntert P. , Wüthrich K. , van Gunsteren W. F. 
Published: May 2005

AbstractStructural and dynamic properties of bovine pancreatic trypsin inhibitor (BPTI) in aqueous solution are investigated using two molecular dynamics (MD) simulations: one of 1.4 ns length and one of 0.8 ns length in which atom‐atom distance bounds derived from NMR spectroscopy are included in the potential energy function to make the trajectory satisfy these experimental data more closely. The simulated properties of BPTI are compared with crystal and solution structures of BPTI, and found to be in agreement with the available experimental data. The best agreement with experiment was obtained when atom‐atom distance restraints were applied in a time‐averaged manner in the simulation. The polypeptide segments found to be most flexible in the MD simulations coincide closely with those showing differences between the crystal and solution structures of BPTI. © 1995 Wiley‐Liss, Inc.