bluuebunny/crossref_metadata_2025_split huggingface dataset:
A vector projection approach to predicting HIV protease cleavage sites in proteins
Authors: Chou Kuo‐Chen , Zhang Chun‐Ting , Kézdy Ferenc J 
Published: May 2005

AbstractA vector projection method is proposed to predict the cleavability of oligopeptides by extended‐specificity site proteases. For an enzyme with eight specificity subsites the substrate octapeptide can be uniquely expressed as a vector in an 8‐dimensional space, whose eight bases correspond to the amino acids at the eight subsites, P1, P1′, P2′, P3′ and P4′, respectively. The component of such a characteristic vector on each of the eight bases is defined as the frequency of an amino acid occurring at a given site. These frequencies were derived from a set of octapeptides known to be cleaved by HIV protease. The cleavability of an octapeptide can then be estimated from the projection of its characteristic vector on an idealized, optimally cleavable vector. The high ratio of correct prediction vs. total prediction for the data in both the training and the testing sets indicates that the new method is self‐consistent and efficient. It provides a rapid and accurate algorithm for analyzing the specificity of any multisubsite enzyme for which there is no coupling between subsites. In particular, it is useful for predicting the cleavability of an oligopeptide by either HIV‐1 or HIV‐2 protease, and hence offers a supplementary means for finding effective inhibitors of HIV protease as potential drugs against AIDS. © Wiley‐Liss, Inc.
A computer model of the interleukin‐4/receptor complex
Authors: Bamborough Paul , Grant Guy H. , Hedgecock Charles J. R. , West Susan P. , Richards W. Graham 
Published: May 2005

AbstractInterleukin‐4 is a member of the cytokine family, a group of related messenger proteins which collectively help to moderate and control the immune response. It is believed that the folding topology of the β‐sheets of the interleukin‐4 receptor (IL4R) is the same as that seen in the crystal structure of CD4. Although the sequence identity is low, homology modeling techniques have been used to model the IL4R structure from CD4. Refinement by molecular dynamics leads to a suggested structure which has been docked to interleukin‐4 (IL4). Several residues of apparent importance for binding are identified. © 1993 Wiley‐Liss, Inc.
A homology model of human interferon α‐2
Authors: Murgolo Nicholas J. , Windsor William T. , Hruza Alan , Reichert Paul , Tsarbopoulos Anthony , Baldwin Samuel , Huang Eric , Pramanik Birendra , Ealick Steven , Trotta Paul P. 
Published: May 2005

AbstractAn atomic coordinate five α‐helix three‐dimensional model is presented for human interferon α‐2 (HuIFNα2). The HuIFNα2 structure was constructed from murine interferon β (MuIFNβ) by homology modeling using the STEREO and IMPACT programs. The HuIFNα2 model is consistent with its known biochemical and biophysical properties including epitope mapping. Lysine residues predicted to be buried in the model were primarily unreactive with succinimidyl‐7‐amino‐4‐methylcoumarin‐3‐acetic acid (AMCA‐NHS), a lysine modification agent, as shown by mass spectrometric analysis of tryptic digests. N‐terminal sequence analysis of polypeptides generated by limited digestion of HuIFNα2 with endoproteinase Lys‐C demonstrated rapid cleavage at K31, which is consistent with the presence of this residue in a loop in the proposed HuIFNα2 model. Based on this model structure potential receptor binding sites are identified. © 1993 Wiley‐Liss, Inc.
Structural analysis of the zinc hydroxide–Thr‐199–Glu‐106 hydrogen‐bond network in human carbonic anhydrase II
Authors: Xue Yafeng , Liljas Anders , Jonsson Bengt‐Harald , Lindskog Sven 
Published: May 2005

AbstractThe singnificance of the zinc hydroxide–Thr‐199–Glu‐106 hydrogen‐bond network in the active site of human carbonic anhydrase II has been examined by X‐ray crystallographic analyses of site‐specific mutants. Mutants with Ala‐199 and Ala‐106 or Gln‐106 have low catalytic activities, while a mutant with Asp‐106 has almost full CO2 hydration activity. The structures of these four mutants, as well as that of the bicarbonate complex of the mutant with Ala‐199, have been determined at 1.7 to 2.2 Å resolution. Removal of the γ atoms of residue 199 leads to distorted tetrahedral geometry at the zine ion, and a catalytically important zinc‐bound water molecule has moved towards Glu‐106. In the bicarbonate complex of the mutant with Ala‐199 one oxygen atom from bicarbonate binds to zinc without displacing this water molecule. Tetrahedral coordination geometries are retained in the mutants at position 106. The mutants with Ala‐106 and Gln‐106 have a zinc‐bound sulfate ion, whereas this sulfate site is only partially occupied in the mutant with Asp‐106. The hydrogen‐bond network seems to be “reversed” in the mutants with Ala‐106 and Gln‐106. The network is preserved as in native enzyme in the mutant with Asp‐106 but the side chain of Asp‐106 is more extended than that of Glu‐106 in the native enzyme. These results illustrate the importance of Glu‐106 and Thr‐199 for controlling the precise coordination geometry of the zinc ion and its ligand preferences with results in an optimal orientation of a zine‐bound hydroxide ion for an attack on the CO2 substrate. © 1993 Wiley‐Liss, Inc.
Crystal structure of TGF‐β2 refined at 1.8 Å resolution
Authors: Daopin Sun , Li Mi , Davies David R. 
Published: May 2005

AbstractThe crystal structure of TGF‐β2 has been refined using data collected with synchrotron radiation (CHESS) to 1.8 Å resolution with a residual R (= ∑ | |Fo| − |Fc| | /∑ |Fo|) factor of 17.3%. The model consists of 890 protein atoms from all 112 residues and 59 water molecules. The monomer of TGF‐β2 assumes a rather extended conformation and lacks a well‐defined hydrophobic core. Surface accessibility calculations show only 44% of the nonpolar surface is buried in the monomer. In contrast, 55.8% of the nonpolar surface area is buried when the two monomers from a dimer, a typical value for globular proteins. This includes a 1300 Å2 buried interface area that is largely hydrophobic. Sequence comparisons using a profile derived from the refined TGF‐β2 structure suggest that the cluster of four disulfides (three intramonomeric disulfide bonds 15–78, 44–109, 48–111 forming a disulfide knot, and one intermonomeric disulfide 77–77) together with the extended β strand region constitutes the conserved structural motif for the TGF‐β superfamily. This structural motif, without the 77–77 disulfide bond, defines also the common fold for a general family of growth factors, including the nerve growth factor and platelet‐derived growth factor families. The fold is conserved only at the monomer level, while the active forms are dimers, suggesting that dimerization plays an important role in regulating the binding of these cytokines to their receptors and in modulating the biological responses. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Crystallographic studies and primary structure of the antitumor monoclonal CC49 Fab′
Authors: Abergel Chantal , Padlan Eduardo A. , Kashmiri Syed V. S. , Milenic Diane , Calvo Benjamin , Schlom Jeffrey 
Published: May 2005

AbstractThe Fab′ of CC49, a murine monoclonal antibody directed against the human tumor‐associated antigen TAG‐72 has been crystallized. The crystals are monoclinic, space group P21 with cell parameters a = 115.6 Å, b = 116.4 Å, and c = 70.3 Å; β = 97.8°. The size of the unit cell is compatible with four Fab′ molecules in the asymmetric unit. The Fab molecules are related by two approximately perpendicular pseudo‐2‐fold axes. One pseudo‐2‐fold axis is parallel to the crystallographic 2‐fold axis and was found by inspection of the Harker section of the native Patterson map; the other was found by a self rotation function. The primary structures of the variable regions of the CC49 antibody light and heavy chains have been determined and are compared with those of the related antitumor antibody B72.3. © 1993 Wiley‐Liss, Inc.
The enzymatic mechanism of carboxypeptidase: A molecular dynamics study
Authors: Banci Lucia , Bertini Ivano , La Penna Giovanni 
Published: May 2005

AbstractAn MD simulation of the system carboxypeptidase A (CPA) with the tetrapeptide Val‐Leu‐Phe‐Phe has been performed in order to learn about the substrate disposition just prior to nucleophilic attack. We have explored the model in which the substrate does not substitute the zinc‐coordinated water (the “water” mechanism). The simulations do suggest as feasible that the Zn‐OH2 group performs a nucleophilic attack on the Phe‐Phe peptidic bond. We have also investigated the model in which the carbonyl oxygen displaces the zinc‐coordinated water. In this case the substrate and Glu‐270 orient themselves to allow an anhydride intermediate during the peptidic bond cleavage (the “anhydride” mechanism). Based on the results of the simulations, both “water” and “anhydride” mechanisms are structurally feasible, although the former model seems more probable on chemical grounds. © 1994 John Wiley & Sons, Inc.
Solution structure of a core peptide derived from scyllatoxin
Authors: Pagel Mark D. , Wemmer David E. 
Published: May 2005

AbstractAn analysis of the sequences of scyllatoxin and charybdotoxin suggested that it would be possible to design a core peptide sequence which would still fold to give the β‐hairpin and helix seen in the toxins, but which would eliminate one disulfide and connecting residues. The core sequence was modeled, then synthesized and purified. The cysteines oxidize in air to give the same disulfide pairings as seen in the parent toxins as the major product. The three‐dimensional structure of the core sequence peptide, termed Max, was determined using proton NMR spectroscopy and found to be identical in secondary structure to the toxins. However differences were found in the relative orientation of the β‐hairpin and helix. The use of this structural motif, found in many insect toxins, as a disulfide framework for exploring sequence/structure/activity relationships is discussed. © 1994 John Wiley & Sons, Inc.
A simplified amino acid potential for use in structure predictions of proteins
Authors: Wallqvist A. , Ullner M. 
Published: May 2005

AbstractABSTRACT A simplified description and a corresponding force field for polypeptides is introduced. Each amino acid residue is reduced to one interaction site, representing the backbone, and one or two side chain sites depending on its size and complexity. Site–site interactions are parameterized after a hydrophobicity criterium. The treatment of backbone sites is in addition designed to reproduce typical polypeptide hydrogen bonding patterns, as well as yielding conformations in accord with the allowed ϕ and ψ angles through an effective angle potential. There are no explicit charges in the model. The derived energy functions, which are based on thermodynamic data and sterical consideration of allowed backbone conformations, correspond to the introduction of an effective potential. The model is tested on two small proteins, avian pancreatic polypeptide and a parathyroid hormone‐related protein, by simulating folding from an initially extended state using Monte Carlo methods. The reduced amino acid description is able to satisfactorily reproduce the experimentally determined native structures. © 1994 John Wiley & Sons, Inc.
Monte carlo simulations of protein folding. II. Application to protein A, ROP, and crambin
Authors: Kolinski Andrzej , Skolnick Jeffrey 
Published: May 2005

AbstractThe hierarchy of lattice Monte Carlo models described in the accompanying paper (Kolinski, A., Skolnick, J. Monte Carlo simulations of protein folding. I. Lattice model and interaction scheme. Proteins 18:338–352, 1994) is applied to the simulation of protein folding and the prediction of 3‐dimensional structure. Using sequence information alone, three proteins have been successfully folded: the B domain of staphylococcal protein A, a 120 residue, monomeric version of ROP dimer, and crambin. Starting from a random expanded conformation, the model proteins fold along relatively well‐defined folding pathways. These involve a collection of early intermediates, which are followed by the final (and rate‐determining) transition from compact intermediates closely resembling the molten globule state to the native‐like state. The predicted structures are rather unique, with native‐like packing of the side chains. The accuracy of the predicted native conformations is better than those obtained in previous folding simulations. The best (but by no means atypical) folds of protein A have a coordinate rms of 2.25 Å from the native Cα trace, and the best coordinate rms from crambin is 3.18 Å. For ROP monomer, the lowest coordinate rms from equivalent Cαs of ROP dimer is 3.65 Å. Thus, for two simple helical proteins and a small α/β protein, the ability to predict protein structure from sequence has been demonstrated. © 1994 John Wiley & Sons, Inc.
Lobster enolase crystallized by serendipity
Authors: Duquerroy S. , Le Bras G. , Janin J. 
Published: May 2005

AbstractAn unknown protein crystallized from a lobster muscle preparation in which arginine kinase was the majority component. It was identified as enolase by peptide sequencing and activity testing, and a SIRAS electron density map showed its three‐dimensional structure to be very similar to that of yeast enolase. © 1994 John Wiley & Sons, Inc.
Preliminary x‐ray analysis of Escherichia coli GMP synthetase: Determination of anomalous scattering factors for a cysteinyl mercury derivative
Authors: Tesmer John J. G. , Stemmler Tim L. , Penner‐Hahn James E. , Jo Davisson V. , Smith Janet L. 
Published: May 2005

AbstractWe have initiated a project to determine the three‐dimensional structure of GMP synthetase (GMPS) from Escherichia coli. GMPS catalyzes the conversion of XMP to GMP in the final step of de novo guanine nucleotide biosynthesis, and is a member of the glutamine amidotransferase family: a group of enzymes responsible for the assimilation of nitrogen into compounds such as amino acids, purine and pyrimidine bases, amino sugars, and antibiotics. The E. coli guaA gene encoding GMPS was cloned into a tac expression vector, overexpressed, and its gene product purified. Conditions for the growth of protein crystals were developed using recombinant GMPS in the presence of MgCl2, ATP, and XMP. The crystals are monoclinic, space group P21, with cell parameters of a = 156.0 Å, b = 102.0 Å, c = 78.8 Å, β= 96.7°. Diffraction data to 2.8 Å spacings were collected on a Xuong‐Hamlin area detector with an overall Rsym of 5.2%. Both the volume of the unit cell and the peaks in the self‐rotation function are consistent with one GMPS tetramer of D2 symmetry in the crystallographic asymmetric unit. Previously, GMPS has been observed only as a dimer in solution. GMPS was covalently modified with p‐chloromercuribenzylsulfonic acid (PCMBS), and its X‐ray fluorescence spectrum was measured through the LIII absorption edge of mercury Anomalous scattering factors for cysteinyl mercury were derived from this spectrum, and the feasibility of structure determination by multi‐wavelength anomalous diffraction was evaluated. The optimal MAD dispersive signal is 4.5% of |F|, and the optimal MAD Bijvoet signal is 7.5% of |F| at a concentration of approximately 1 mercury per 10‐kDa protein. The anomalous scattering factors tabulated here should be transferable to cysteinyl mercury in other proteins. © 1994 John Wiley & Sons, Inc.
Expression, purification, and crystallization of restriction endonuclease PvuII with DNA containing its recognition site
Authors: Balendiran K. , Bonventre Joseph , Knott Roger , Jack William , Benner Jack , Schildkraut Ira , Anderson John E. 
Published: May 2005

AbstractWe have overexpressed the type II restriction endonuclease PvuII (R.PvuII) in E. coli, prepared large amounts of the homogeneous enzyme, and crystallized it with an oligonucleotide carrying a PvuII recognition site. The cocrystals are orthorhombic space group P212121 with cell constants a = 95.8 Å, b = 86.3 Å, c = 48.5 Å, and diffract X‐rays to at least 2.7 Å. There is a complex of two protein subunits and one oligonucleotide duplex in the asymmetric unit. © 1994 Wiley‐Liss, Inc.
Energy minimization method using automata network for sequence and side‐chain conformation prediction from given backbone geometry
Authors: Kono Hidetoshi , Doi Junta 
Published: May 2005

AbstractGlobular proteins have high packing densities as a result of residue side chains in the core achieving a tight, complementary packing. The internal packing is considered the main determinant of native protein structure. From that point of view, we present here a method of energy minimization using an automata network to predict a set of amino acid sequences and their side‐chain conformations from a desired backbone geometry for de novo design of proteins. Using discrete side‐chain conformations, that is, rotamers, the sequence generation problem from a given backbone geometry becomes one of combinatorial problems. We focused on the residues composing the interior core region and predicted a set of amino acid Sequences and their side‐chain conformations only from a given backbone geometry. The kinds of residues were restricted to six hydrophobic amino acids (Ala, Ile, Met, Leu, Phe, and Val) because the core regions are almost always composed of hydrophobic residues. The obtained sequences were well packed as was the native sequence. The method can be used for automated sequence generation in the de novo design of proteins. © 1994 Wiley‐Liss, Inc.
Molecular basis of cooperativity in protein folding. V. Thermodynamic and structural conditions for the stabilization of compact denatured states
Authors: Xie Dong , Freire Ernesto 
Published: May 2005

AbstractThe heat‐denatured state of proteins has been usually assumed to be a fully hydrated random coil. It is now evident that under certain solvent conditions or after chemical or genetic modifications, the protein molecule may exhibit a hydrophobic core and residual secondary structure after thermal denaturation. This state of the protein has been called the “compact denatured” or “molten globule” state. Recently is has been shown that α‐lactalbumin at pH < 5 denatures into a molten globule state upon increasing the temperature (Griko, Y., Freire, E., Privalov, P. L. Biochemistry 33:1889–1899, 1994). This state has a lower heat capacity and a higher enthalpy at low temperatures than the unfolded state. At those temperatures the stabilization of the molten globule state is of an entropic origin since the enthalpy contributes unfavorably to the Gibbs free energy. Since the molten globule is more structured than the unfolded state and, therefore, is expected to have a lower configurational entropy, the net entropic gain must originate primarily from solvent related entropy arising from the hydrophobic effect, and to a lesser extent from protonation or electrostatic effects. In this work, we have examined a large ensemble of partly folded states derived from the native structure of α‐lactalbumin in order to identify those states that satisfy the energetic criteria of the molten globule. It was found that only few states satisfied the experimental constraints and that, furthermore, those states were part of the same structural family. In particular, the regions corresponding to the A, B, and C helices were found to be folded, while the β sheet and the D helix were found to be unfolded. At temperatures below 45°C the states exhibiting those structural characteristics are enthalpically higher than the unfolded state in agreement with the experimental data. Interestingly, those states have a heat capacity close to that observed for the acid pH compact denatured state of α‐lactalbumin [980 cal (mol.K)−l]. In addition, the folded regions of these states include those residues found to be highly protected by NMR hydrogen exchange experiments. This work represents an initial attempt to model the structural origin of the thermodynamic properties of partly folded states. The results suggest a number of structural features that are consistent with experimental data. © 1994 Wiley‐Liss, Inc.
Helix‐capping interaction in λ cro protein: A free energy simulation analysis
Authors: Tidor Bruce 
Published: May 2005

AbstractThe stability mutant Tyr‐26 → Asp was studied in the Cro protein from bacteriophage λ using free energy molecular dynamics simulations. The mutant was calculated to be more stable than the wild type by 3.0 ± 1.7 kcal/mol/monomer, in reasonable agreement with experiment (1.4 kcal/mol/monomer). Moreover, the aspartic acid in the mutant was found to form a capping interation with the amino terminus of the third α‐helix of Cro. The simulations were analyzed to understand better the source of the stability of this helix‐capping interaction and to examine the results in light of previous explanations of stabilizing helix caps‐namely, a model of local unsatisfied hydrogen bonds at the helix termini and the helix macro dipole model. Analysis of the simulations shows that the stabilizing effect of this charged helical cap is due both to favorable hydrogen bonds with backbone NH groups at the helix terminus and to favorable electrostatic interactions (but not hydrogen bonds) with their carbonyls (effectively the next row of local dipoles in the helix). However, electrostatic interactions are weak or negligible with backbone dipolar groups in the helix further away from the terminus. Moreover, the importance of other local electrostatic interactions with polar side chains near the helix terminus, which are neglected in most treatments of this effect, are shown to be important. Thus, the results support a model that is intermediate between the two previous explanations: both unsatisfied hydrogen bonds at the helix terminus and other, local preoriented dipolar groups stabilize the helix cap. These findings suggest that similar interactions with preoriented dipolar groups may be important for cooperativity in other charge–dipole interactions and may be employed to advantage for molecular design. © 1994 Wiley‐Liss, Inc.
Crystallization of a scRIP—gelonin isolated from plant seeds Gelonium multiforum
Authors: Satyamurty P. , Hosur M. V. , Misquith S. , Surolia A. , Kannan K. K. 
Published: May 2005

AbstractSingle crystals of the protein gelonin isolated from the seeds of Gelonium multiforum have been grown at room temperature by vapor diffusion method. The crystals are monclinic with a = 49.4 Å, b = 44.9 Å, c = 137.4 Å, and β = 98.3°. The space group is P21, with two molecules in the asymmetric unit which are related by a noncrystallographic 2‐fold axis along ψ =13° and ϕ =88°. The crystals diffract X‐rays to high resolution, making it possible to obtain an accurate structure of this single chain ribosome inactivating protein. © 1994 Wiley‐Liss, Inc.