bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary structural predictions for the clostridial neurotoxins
Authors: Lebeda Frank J. , Olson Mark A. 
Published: May 2005

AbstractThe primary structures of a family of ten clostridial. Neurotoxins have recently been deduced yet little information is presently available concerning their secondary or tertiary structures. Because the overall similarity percentage of multiply aligned sequences is high, the secondary structures of these metalloendopeptidases are also expected to be conserved. The neural net program, PHD (Rost and Sander, Proc. Natl. Acad. Sci. USA 90:7558–7562, 1993), predicted that the secondary structures of the neurotoxins were indeed conserved in both single and multiple sequence modes of analysis. Predictions for the amounts of helical, extended, and loop states from the single sequence analyses were consistent with previously published data from circular dichroism studies on some of these neurotoxins. In the single analysis mode, only the aligned regions were predicted to show conservation of the three‐state structure. In contrast, the multiple sequence analysis predicted that a conserved state (variable loops) also exists in non‐aligned regions. Alignments with the primary structure of the prototypic metalloendopeptidase thermolysin showed that about 25% of the residues within this enzyme are similar to those in the neurotoxins. A comparison of thermolysin's known secondary structure with the predictions from this study showed that about 80% of thermolysin's residues could be structurally aligned with those in the neurotoxins. These predictions provide the necessary. Framework to build a homologous low‐resolution tertiary structure of the neurotoxin active site that will be essential in the development of synthetic inhibitors. © 1994 Wiley‐Liss, Inc.
Elusive affinities
Authors: Janin Joël 
Published: May 2005

AbstractThe affinity of two molecules for each other and its temperature dependence are determined by the change in enthalpy, free enthalpy, entropy, and heat capacity upon dissociation. As we know the forces that stabilize‐protein–protein or protein–DNA association and the three‐dimensional structures of the complex, we can in principle derive values for each one of these parameters. The calculation is done first in gas phase by molecular mechanics, then in solution with the help of hydration parameters calibrated on small molecules. However, estimates of enthalpy and entropy changes in gas phase have excessively large error bars even under the approximation that the components of the complex associate as rigid bodies. No reliable result can be expected at the end. The fit to experimental values derived from binding and calorimetric measurements is poor, except for the dissociation heat capacity. This parameter can be attributed mostly to the hydration step and it correlates with the size of the interface. Many protein–protein complexes have interface areas in the range 1200–2000 Å2 and only small conformation changes, so the rigid body approximation applies. It is less generally valid in protein–DNA complexes, which have interfaces covering 2200–3100 Å2, large dissociation heat capacities, and affect both the conformation and the dynamics of their components. © 1995 Wiley‐Liss, Inc.
Molecular dynamics simulations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion
Authors: Ryde Ulf 
Published: May 2005

AbstractA detailed parameterization is presented of a zinc ion with one histidine and two cysteinate ligands, together with one or two water, hydroxide, aldehyde, alcohol, or alkoxide ligands. The parameterization is tailored for the active site of alcohol dehydrogenase and is obtained entirely from quantum chemical computations. The force‐field reproduces excellently the geometry of quantum chemically optimized zinc complexes as well as the crystallographic geometry of the active site of alcohol dehydrogenase and small organic structures. The parameterization is used in molecular dynamics simulations and molecular mechanical energy minimizations of alcohol dehydrogenase with a four‐ or five‐coordinate catalytic zinc ion. The active‐site zinc ion seems to prefer four‐coordination over five‐coordination by at least 36 kJ/mol. The only stable binding site of a fifth ligand at the active‐site zinc ion is opposite to the normal substrate site, in a narrow cavity behind the zinc ion. Only molecules of the size of water or smaller may occupy this site. There are large fluctuations in the geometry of the zinc coordination sphere. A four‐coordinate water molecule alternates frequently (every 7 ps) between the substrate site and the fifth binding site and even two five coordinate water molecules may interchange ligation sites without prior dissociation. Ligand exchange at the zinc ion probably proceeds by a dissociative mechanism. The results show that it is essential to allow for bond stretching degrees of freedom in molecular dynamics simulations to get a correct description of the dynamics of the metal coordination sphere; bond length constraints may restrict the accessible part of the phase space and therefore lead to qualitatively erroneous results. © 1995 Wiley‐Liss, Inc.
Modulation of DNA‐binding specificity within the nuclear receptor family by substitutions at a single amino acid position
Authors: Zilliacus Johanna , Wright Anthony P. H. , Carlstedt‐Duke Jan , Nilsson Lennart , Gustafsson Jan‐Åke 
Published: May 2005

AbstractRegulation of gene expression involves a large number of transcription factors with unique DNA‐binding properties. Many transcription factors belong to families of related proteins that bind to similar but distinct sequences. In this study we have analyzed how amino acid substitutions at a single position in the DNA‐binding domain modulate the DNA binding specificity within the nuclear receptor family of transcription factors. All possible amino acids were introduced at the first position in the DNA recognition helix, and the specificities of the mutants were analyzed using response elements containing all combinations of bases at two variable base pair positions. All mutant proteins were functional in DNA binding, and could be divided into classes of mutants with different response element specificities. By combining functional data with analysis of the structural effects of the mutations by molecular modeling, we could identify both prohibitive steric interactions as well as positive interactions, such as hydrogen bonds, that function as important determinants for specificity. Only the residues found naturally in the glucocorticoid and estrogen receptors, glycine and glutamate, produce unique binding specificities. The specificities of the other mutants overlap with each other somewhat but the substitutions clearly have potential to contribute to diversity within the nuclear receptor family. © 1995 Wiley‐Liss, Inc.
Three‐dimensional structure prediction of the NAD binding site of proton‐pumping transhydrogenase from Escherichia coli
Authors: Fjellström Ola , Olausson Torbjörn , Hu Xiang , Källebring Bruno , Rydström Jan , Ahmad Suhail , Bragg Philip D. 
Published: May 2005

AbstractA three‐dimensional structure of the NAD site of Escerichia coli transhydrogenase has been predicted. The model is based on analysis of conserved residues among the transhydrogenases from five different sources, homologies with enzymes using NAD as cofactors or substrates, hydrophilicity profiles, and secondary structure predictions. The present model supports the hypothesis that there is one binding site, located relatively close to the N‐terminus of the α‐subunit. The proposed structure spans residues α145 to α287, and it includes five β‐strands and five α‐helices oriented in a typical open twisted α/β conformation. The amino acid sequence following the GXGXXG dinucleotide binding consensus sequence (residues α172 to α177) correlates exactly to a typical fingerprint region for ADP binding βαβ folds in dinucleotide binding enzymes. In the model, aspartic acid α195 forms hydrogen bonds to one or both hydroxyl groups on the adenosine ribose sugar moiety. Threonine α196 and alanine α256, located at the end of βB and βD, respectively, create a hydrophobic sandwich with the adenine part of NAD buried inside. The nicotinamide part is located in a hydrophobic cleft between αA and βE. Mutagenesis work has been carried out in order to test the predicted model and to determine whether residues within this domain are important for proton pumping directly. All data support the predicted structure, and no residue crucial for proton pumping Was detected. Since no three‐dimensional structure of transhydrogenase has been solved, a well based tertiary structure prediction is of great value for further experimental design in trying to elucidate the mechanism of the energy‐linked proton pump. © 1995 Wiley‐Liss, Inc.
A new protein folding recognition potential function
Authors: Wang Yanli , Lai Luhua , Han Yuzhen , Xu Xiaojie , Tang Youqi 
Published: May 2005

AbstractOn the study of protein inverse folding problem, one goal is to find simple and efficient potential to evaluate the compatibility between structure and a given sequence. We present here a novo empirical mean force potential to address the importance of electrostatic interactions in protein inverse folding study. It is based on protein main chain polar fraction and constructed in a way similar with Sippl's from a database of 64 known independent three‐dimensional protein structures. This potential was applied to recognize the protein native conformations among a conformation pool. Calculated results show that this potential is powerful in picking out native conformations, in addition it can also find structure similarity between proteins with low sequence similarity. The success of this new potential clearly shows the importance of electrostatic factors in protein inverse folding studies. © 1995 Wiley‐Liss, Inc.
Accurate general method for lattice approximation of three‐dimensional structure of a chain molecule
Authors: Rykunov Dmitry S. , Reva Boris A. , Finkelstein Alexey V. 
Published: May 2005

AbstractAn algorithm based on dynamic programming gives the lattice models having the minimal RMS deviations from the actual folds of protein (RNA, etc.) chains for a given lattice and a given orientation of the macromolecule relative to the lattice. The algorithm is applicable for 3‐D lattices of any kind. The accuracy of the lattice approximation increases when the distance between neighbor chain links is not rigidly fixed. Special repulsive potentials facilitate generation of self‐avoiding lattice chains. The results of model building show the efficiency and precisionof this proposed general method when compared with others. © 1995 Wiley‐Liss, Inc.
Exploring the binding preferences/specificity in the active site of human cathepsin E
Authors: Rao‐Naik Chetana , Guruprasad Kunchur , Batley Brian , Rapundalo Stephen , Hill Jeffrey , Blundell Tom , Kay John , Dunn Ben M. 
Published: May 2005

AbstractAspartic proteinases are produced in the human body by a variety of cells. Some of these proteins, examples of which are pepsin, gastricsin, and renin, are secreted and exert their effects in the extracellular spaces. Cathepsin D and cathepsin E on the other hand are intracellular enzymes. The least characterized of the human aspartic proteinases is cathepsin E. Presented here are results of studies designed to characterize the binding specificities in the active site of human cathepsin E with comparison to othermechanistically similar enzymes. A peptide series based on Lys‐Pro‐Ala‐Lys‐Phe*Nph‐Arg‐Leu was generatedto elucidate the specificity in the individual binding pockets with systematic substitutions in the P5− P2 and P2′‐P3′ based on charge, hydrophobicity, and hydrogen bonding. Also, to explore the S2 binding preferences, asecond series of peptides based on Lys‐Pro‐Ile‐Glu‐Phe*Nph‐Arg‐Leu was generated with systematic replacements in the P2 position. Kinetic parameters were determined forboth sets of peptides. The results were correlated to a rule‐based structural model of human cathepsin E, constructed on the known three‐dimensional structures of several highly homologous aspartic proteinases; porcine pepsin, bovine chymosin, yeast proteinase A, human cathepsin D, andmouse and human renin. Important specificity‐determining interactions were found in the S3 (Glu13) and S2 (Thr‐222, Gln‐287, Leu‐289, Ile‐300)subsites. © 1995 Wiley‐Liss, Inc.
Comparison of the effects of hydrophobicity, amphiphilicity, and α‐helicity on the activities of antimicrobial peptides
Authors: Pathak Naveen , Salas‐Auvert Rodolfo , Ruche Gaël , Janna Marie‐hélène , McCarthy David , Harrison Roger G. 
Published: May 2005

AbstractMultiple linear regression was used to quantify the dependence of the antimicrobial activity of 13 peptides upon three calculated or experimentally determined parameters: mean hydrophobicity, mean hydrophobic moment, and α‐helix content. Mean hydrophobic moment is a measure of the amphiphilicity of peptides in an α‐helical conformation. Antimicrobial activity was quantified as the reciprocal of the measured minimal inhibitory concentration (MIC) against Escherichia coli. One of the peptides was magainin 2, and the remainder were novel peptides designed for this study. The multiple linear regression results revealed that the amphiphilicity of the peptides was the most important factor governing anti‐microbial activity compared to mean hydrophobicity orα‐helix content. A better regression cf the data was obtained using In(1/MIC + constant) as the dependent variable than with either 1/MIC or In(1/MIC). These results should be useful in designing peptides with higher antimicrobial activity. © 1995 Wiley‐Liss, Inc.
Crystallization and preliminary X‐ray investigation of recombinant human interleukin 10
Authors: Cook William J. , Windsor William T. , Murgolo Nicholas J. , Tindall Stephen H. , Nagabhushan Tattanahalli L. , Walter Mark R. 
Published: May 2005

AbstractCrystals of recombinant human interleukin 10 have been grown from solutions of ammonium sulfate. The crystals are tetragonal, space group P41212 or P43212; the unit cell axes are a = 36.5 Å and c = 221.9 Å. There is the equivalent of one polypeptide chain in the asymmetric unit. The crystals are stable to X‐rays and diffract to at least 2.5 Å resolution. © 1995 Wiley‐Liss, Inc.
Prediction of the structure of GroES and its interaction with GroEL
Authors: Valencia Alfonso , Hubbard Tim J. , Muga Arturo , Bañuelos Sonia , Llorca Oscar , Carrascosa José L. , Valpuesta José Marí 
Published: May 2005

AbstractThe three‐dimensional structure of the GroES monomer and its interaction with GroEL has been predicted using a combination of prediction tools and experimental data obtained by biophysical [electron microscope (EM), Fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR)] and biochemical techniques. The GroES monomer, according to the prediction, is composed of eight β‐strands forming a β‐barrel with loose ends. In the model, β‐strands 5–8 run along the outer surface of GroES, forming an antiparallel β‐sheet with β4 loosely bound to one of the edges. β‐strands 1–3 would then be parallel and placed in the interior of the molecule. Loops 1–3 would face the internal cavity of the GroEL–GroES complex, and together with conserved residues in loops 5 and 7, would form the active surface interacting with GroEL. © 1995 Wiley‐Liss, Inc.
The catalytic domain of a bacterial lytic transglycosylase defines a novel class of lysozymes
Authors: Thunnissen Andy‐Mark W. H. , Isaacs Neil W. , Dijkstral Bauke W. 
Published: May 2005

AbstractThe 70‐kDa soluble lytic transglycosylase (SLT70) from Escherichia coli is a bacterial exo‐muramidase that cleaves the cell wall peptidoglycan, producing 1,6‐anhydro‐muropeptides. The X‐ray structure of SLT70 showed that one of its domains is structurally related to lysozyme, although there is no obvious similarity in amino acid sequence. To relate discrete structural features to differences in reaction mechanism and substrate/product specificity, we compared the threedimensional structure of the catalytic domain of SLT70 with the structures of three typical representatives of the lysozyme superfamily: chicken‐type hen egg‐white lysozyme, goosetype swan egg‐white lysozyme, and phage‐type lysozyme from bacteriophage T4. We find a particularly close relationship between the catalytic domain of SLT70 and goose‐type lysozyme, with not only a significant similarity in overall structure, but even a weak homology in amino acid sequence. This finding supports the notion that the goose‐type lysozyme takes up a central position in the lysozyme superfamily and that it is structurally closest to the lysozyme ancestors. The saccharide‐binding groove is the most conserved part in the four structures, but only two residues are absolutely preserved: the “catalytic” glutamic acid and a structurally required glycine. The “catalytic” aspartate is absent in SLT70, a difference that can be related to a different mechanism of cleavage of the β‐1,4‐glycosidic bond. The unique composition of amino acids at the catalytic site, and the observation of a number of differences in the arrangements of secondary structure elements, define the catalytic domain of SLT70 as a novel class of lysozymes. Its fold is expected to be exemplary for other bacterial and bacteriophage muramidases with lytic transglycosylase activity. © 1995 Wiley‐Liss, Inc.
Crystallization of Thermus thermophilus histidyl‐tRNA synthetase and Its complex with tRNAHis
Authors: Yaremchuk A. D. , Cusack S. , Åberg A. , Gudzera O. , Kryklivyi I. , Tukalo M. 
Published: May 2005

AbstractHistidyl‐tRNA synthetase (HisRS) has been purified from the extreme thermophile Thermus thermophilus. The protein has been crystallized separately with histidine and with its cognate tRNAHis. Both crystals have been obtained using the vapor diffusion method with ammonium sulphate as precipitant. The crystals of HisRS with histidine belong to the spacegroup P21212 with cell parameters a = 171.3 Å, b = 214.7 Å, c = 49.3 Å, α = β = γ = 90°. A complete data set to a resolution of 2.7Å with an Rmerge on intensities of 4.1% has been collected on a single frozen crystal. A partial data set collected on a crystal of HisRS in complex with tRNAHis shows that the crystals are tetragonal with cell parameters a = b = 232 Å, c = 559 Å, α = β = γ = 90° and diffract to about 4.5 Å resolution. © 1995 Wiley‐Liss, Inc.
Rigid domains in proteins: An algorithmic approach to their identification
Authors: Nichols William L. , Rose George D. , Ten Eyck Lynn F. , Zimm Bruno H. 
Published: May 2005

AbstractA rigid domain, defined here as a tertiary structure common to two or more different protein conformations, can be identified numerically from atomic coordinates by finding sets of residues, one in each conformation, such that the distance between any two residues within the set belonging to one conformation is the same as the distance between the two structurally equivalent residues within the set belonging to any other conformation. The distance between two residues is taken to be the distance between their respective α carbon atoms. With the methods of this paper we have found in the deoxy and oxy conformations of the human hemoglobin α1β1 dimer a rigid domain closely related to that previously identified by Baldwin and Chothia (J. Mol. Biol. 129:175–220,1979). We provide two algorithms, both using the difference‐distance matrix, with which to search for rigid domains directly from atomic coordinates. The first finds all rigid domains in a protein but has storage and processing demands that become prohibitively large with increasing protein size. The second, although not necessarily finding every rigid domain, is computationally tractable for proteins of any size. Because of its efficiency we are able to search protein conformations recursively for groups of non‐intersecting domains. Different protein conformations, when aligned by superimposing their respective domain structures; can be examined for structural differences in regions complementing a rigid domain. © 1995 Wiley‐Liss, Inc.
Characterization of crystals of the thermostable DNA polymerase I from thermus aquaticus
Authors: Urs Usha K. , Sharkey David J. , Peat Thomas S. , Hendrickson Wayne A. , Krishna Murthy H. M. 
Published: May 2005

AbstractThermus aquaticus DNA polymerase I is an enzyme that is of both physiological and technological interest. It carries out template‐directed polymerization of DNA at elevated temperatures and is widely used in polymerase chain reaction (PCR). We have obtained crystals of the enzyme that diffracts X‐rays to at least 3.0 Å resolution in a cubic space group. Determination of the three‐dimensional structure of the native enzyme along with those of relevant complexes will greatly enhance our knowledge of molecular events involved in DNA replication, will permit improvements in PCR, and will add to our knowledge of the structural bases of thermo stability in proteins. © 1995 Wiley‐Liss, Inc.
Structural superposition of proteins with unknown alignment and detection of topological similarity using a six‐dimensional search algorithm
Authors: Diederichs Kay 
Published: May 2005

AbstractAn algorithm for the rigid‐body superposition of proteins is described and tested. No prior knowledge of equivalent residues is required. To find the common structural core of two proteins, an exhaustive grid search is conducted in three‐dimensional angle space, and at each grid point a fast translation search in three‐dimensional space is performed. The best superposition at a given angle set is defined by that translation vector which maximizes the weighted number of equivalent Cα atoms. Filters using the information about the sequential character of the polypeptide chain are employed to identify that rotation and translation which yields the highest topological similarity of the two proteins. The algorithm is shown to find the best superposition of distantly related structures, and to be capable of finding similar structures to a given atomic model in the Brookhaven Protein Data Bank. In a search using granulocyte‐macrophage colony‐stimulating factor as a template, all other four‐helix bundle cytokines with up‐up‐down‐down topology were found to give the highest values of a topological similarity score, followed by interferon‐β and ‐γ and those four‐helix bundles with the more common up‐down‐up‐down topology. In another example, the insertion domain of the long variant adenylate kinases is demonstrated to share its fold with rubredoxin. © 1995 Wiley‐Liss, Inc.