bluuebunny/crossref_metadata_2025_split huggingface dataset:
The high‐resolution crystal structure of porcine pepsinogen
Authors: Hartsuck Jean A. , Koelsch Gerald , Remington S. James 
Published: May 2005

AbstractThe structure of porcine pepsinogen at pH 6.1 has been refined to an R‐factor of 0.173 for data extending to 1.65 Å. The final model contains 180 solvent molecules and lacks density for residues 157–161. The structure of this aspartic proteinase zymogen possesses many of the characteristics of pepsin, the mature enzyme. The secondary structure of the zymogen consists predominantly of β‐sheet, with an approximate 2‐fold axis of symmetry. The activation peptide packs into the active site cleft, and the N‐terminus (IP–9P) occupies the position of the mature N‐terminus (1–9). Thus changes upon activation include excision of the activation peptide and proper relocation of the mature N‐terminus. The activation peptide or residues of the displaced mature N‐terminus make specific interactions with the substrate binding subsites. The active site of pepsinogen is intact; thus the lack of activity of pepsinogen is not due to a deformation of the active site. Nine ion pairs in pepsinogen may be important in the advent of activation and involve the activation peptide or regions of the mature N‐terminus which are relocated in the mature enzyme. The activation peptide–pepsin junction, 44P‐1, is characterized by high thermal parameters and weak density, indicating a flexible structure which would be accessible to cleavage. Pepsinogen is an appropriate model for the structures of other zymogens in the aspartic proteinase family. © 1992 Wiley‐Liss, Inc.
Characterization of HIV‐1 p24 self‐association using analytical affinity chromatography
Authors: Rosé Sergio , Hensley Preston , O'Shannessy Daniel J. , Culp Jeffrey , Debouck Christine , Chaiken Irwin 
Published: May 2005

AbstractAnalytical affinity chromatography (AAC) was used to detect and quantitate the self‐association of p24gag, the major structural capsid protein of human immunodeficiency virus (HIV‐1). p24gag was immobilized on a hydrophilic polymer (methacrylate) chromatographic support. The resulting affinity column was able to interact with soluble p24, as judged by the chromatographic retardation of the soluble protein upon isocratic elution undernonchaotropic binding conditions. The variation of elution volume with soluble protein concentration fit to a monomer–dimer model for self‐association. The soluble p24–immobilized p24 association process was observed using both frontal and zonal elution AAC at varying pH values; the dissociation constant was 3–4 × 10−5 M at pH 7. That p24 monomer associates to dimers was determined in solution using analytical ultracentrifugation. The solution Kd was 1.3 × 10−5 M at pH 7. AAC in the zonal elution mode provides a simple and rapid means to screen for other HIV‐1 macromolecules that may interact with p24 as well as for modulators, including antagonists, of HIV p24 protein assembly. © 1992 Wiley‐Liss, Inc.
Modeling microdomains: The surface area of globin helices
Authors: Weaver David L. 
Published: May 2005

AbstractThe accessible surface areas of 53 high‐resolution globin helices are correlated with molecular weight. The linear fit is assessed for satistical accuracy using a boot‐strap analysis, and by comparison to the areas of 13 ideal polyalanine α‐helices. The accessible area of the unfolded helices is compared with the folded values before helix‐helix packing. An analytical physical model is presented to explain the correlation, and to provide an analytical value for the surface area parameter in the diffusion‐collision model of protein folding. © 1992 Wiley‐Liss, Inc.
Folding in vitro of bovine pancreatic trypsin inhibitor in the presence of proteins of the endoplasmic reticulum
Authors: Zapun André , Creighton Thomas E. , Rowling Pamela J. E. , Freedman Robert B. 
Published: May 2005

AbstractThe rate of folding and disulfide bond formation in reduced BPTI were measured in vitro in the presence and absence of total protein from the endoplasmic reticulum. The rates were increased substantially by the endoplasmic reticulum proteins, but only to the extent expected from the known content and activity of protein–disulfide–isomerase. No effects of added ATP or Ca2+ were observed, even though protein–disulfide–isomerase blinds Ca2+ tightly. © 1992 Wiley‐Liss, Inc.
A structural model for human dihydrolipoamide dehydrogenase
Authors: Jentoft Joyce E. , Shoham Menachem , Hurst Darren , Patel Mulchand S. 
Published: May 2005

AbstractThe hypothesis that dihydrolipoamide dehydrogenases (E3s) have tertiary structures very similar to that of human glutathione reductase (GR) was tested in detail by three separate criteria: (1) by analyzing each putative secondary structural element for conservation of appropriate polar/nonpolar regions, (2) by detailed comparison of putative active site residues in E3s with their authentic counterparts in human GR, and (3) by comparison of residues at the putative dimeric interface of the E3s with the authentic residues in GR. All three criteria are satisfied in a convincing way for the 7 E3s that were considered, supporting the conclusion that the structural scaffolding and the overall tertiary structure (which determines the location of functional sites and residues) are remarkably similar for the E3s and for GR. These analyses together with the crystal structures of human erythrocyte GR formed the basis for construction of a molecular model for human E3. The cofactor FAD and the substrakes NAD and lipoic acid were also included in the model. Unexpectedly, the surface residues in the cleft that holds the lipoamide were found to be highly charged and predominantly acidic, allowing us to predict that the region around the lipoamide in the sub‐unit should be basic in nature. The molecular model can be tested by site‐directed mutagenesis of residues predicted to be in the dihydrolipoamide acetyltransferase subunit binding cleft. © 1992 Wiley‐Liss, Inc.
The role of tyrosine 67 in the cytochrome c heme crevice structure studied by semisynthesis
Authors: Frauenhoff Mary M. , Scott Robert A. 
Published: May 2005

AbstractTyr‐67 of mitochondrial cytochrome c is thought to be involved in important hydrogen bonding interactions in the hydrophobic heme pocket of the protein (Takano, T., Dickerson, R.E. (1981) J. Mol. Biol. 153:95–115). The role of this highly conserved residue in heme pocket stability was studied by comparing properties of semisynthetic (Phe‐67) and (p‐F‐Phe‐67) analogs with those of native cytochrome c and a “control” analog, (Hse‐65)cytochrome c. The (Phe‐67) and (p‐F‐Phe‐67) analogs have well‐developed 695‐nm visible absorption bands and are active in a cytochrome c oxidase assay. The reduction potentials of both analogs are lower than the native protein by approximately 50 mV. Although both analogs bind imidazole with higher affinity than the native protein, only the (p‐F‐Phe‐67) analog has a 3‐ to 5‐fold lower binding constant for cyanide. Only the (Phe‐67) analog was significantly more stable toward alkaline isomerization. These results are not consistent with stabilization of the native protein heme pocket via hydrogen bonding of Tyr‐67 to Met‐80. An alternative steric role for Tyr‐67 is proposed in which the residue controls the heme reduction potential by limiting the number of internal H2O molecules in the heme pocket. © 1992 Wiley‐Liss, Inc.
Selection of a representative set of structures from brookhaven protein data bank
Authors: Boberg Jorma , Salakoski Tapio , Vihinen Mauno 
Published: May 2005

AbstractReliable structural and statistical analyses of three dimensional protein structures should be based on unbiased data. The Protein Data Bank is highly redundant, containing several entries for identical or very similar sequences. A technique was developed for clustering the known structures based on their sequences and contents of α‐and β‐structures. First, sequences were aligned pairwise. A representative sample of sequences was then obtained by grouping similar sequences together, and selecting a typical representative from each group. The similarity significance threshold needed in the clustering method was found by analyzing similarities of random sequences. Because three dimensional structures for proteins of same structural class are generally more conserved than their sequences, the proteins were clustered also according to their contents of secondary structural elements. The results of these clusterings indicate conservation of α‐and β‐structures even when sequence similarity is relatively low.An unbiased sample of 103 high resolution structures, representing a wide variety of proteins, was chosen based on the suggestions made by the clustering algorithm. The proteins were divided into structural classes according to their contents and ratios of secondary structural elements. Previous classifications have suffered from subjectice view of secondary structures, whereas here the classification was based on backbone geometry. The concise view lead to reclassification of some structures. The representative set of structures facilitates unbiased analyses of relationships between protein sequence, function, and structure as well as of structural characteristics. © 1992 Wiley‐Liss, Inc.
Effect of polyethylene glycol‐400 at low concentrations on long‐term growth of muscle phosphoglucomutase crystals from concentrated salt solutions
Authors: Ray William J. 
Published: May 2005

AbstractAlthough rabbit muscle phosphoglucomutase occasionally deposits tetragonal crystals from solutions of ammonium sulfate at about 47% of saturation, low concentrations of polyethylene glycol‐400 (PEG), 1 to 4.5% w/v, must be included to sustain crystal growth. A comparison of long‐term growth rates for macroscopic crystals in the presence and absence of added PEG suggests that at high salt concentration this cosolute exerts its primary effect on disordered protein aggregates, either in the external medium or at the surface of the crystal, and thereby allows the growth of much larger crystals. Since the observed effects may arise from a PEG‐induced increase in the “solubility” of the aggregate that exceeds the induced increase in solubility of the crystalline phase under these conditions, the physical basis for a cosolute‐induced increase in solubility in the presence of a precipitant is considered. The applicability of such a rationale to the present system is supported by an assessment of the relative effects of polyeth‐yiene glycol and β‐octylglucoside on amorphous, salt‐induced precipitates of phosphoglucomutase. PEG also produces what appears to be a differential effect on nucleation efficiency and crystal growth rate. Thus, seed crystals cannot be enlarged at a significant rate at high salt concentration without producing showers of extraneous nucleation centers when the concentration of added PEG is 3% or less. But PEG concentrations of 4.5% essentially eliminate the showering problem, ostensibly by increasing the supersaturation required for nucleation to a greater extent than that required for crystal growth. The same type of effect is observed during de novo growth. Again a solubility‐based mechanism is posed. Hysteretic effects related to properties of amorphous aggregates of the protein also are described. © 1992 Wiley‐Liss, Inc.
Mutagenic dissection of hemoglobin cooperativity: Effects of amino acidalteration on subunit assembly of oxy and deoxy tetramers
Authors: Turner George J. , Galacteros Frederic , Doyle Michael L. , Hedlund Bo , Pettigrew Donald W. , Turner Benjamin W. , Smith Francine R. , Moo‐Penn Winston , Rucknagel Donald L. , Ackers Gary K. 
Published: May 2005

AbstractFree energies of oxygen‐linked subunit assembly and cooperative interaction have been determined for 34 molecular species of human hemoglobin, which differ by amino acid alterations as a result of mutation or chemical modification at specific sites. These studies required the development of extensions to our earlier methodology. In combination with previous results they comprise a data base of 60 hemoglobin species, characterized under the same conditions. The data base was analyzed in terms of the five following issues. (1) Range and sensitivity to site modifications. Deoxy tetramers showed greater average energetic response to structural modifications than the oxy species, but the ranges are similar for the two ligation forms. (2) Structural localization of cooperative free energy. Difference free energies of dimer‐tetramer assembly (oxy minus deoxy) yielded ΔGc for each hemoglobin, i.e., thefree energy used for modulation of oxygen affinity over all four binding steps. A structure‐energy map constructed from these results shows that the α1 β2 interface is a unique structural location of the noncovalent bonding interactions that are energetically coupled to cooperativity. (3) Relationship of cooperativity to intrinsic binding. Oxygen binding energetics for dissociated dimers of mutants strongly indicates that cooperativity and intrinsic binding are completely decoupled by tetramer to dimer dissociation. (4) Additivity, site‐site coupling and adventitious perturbations. All these are exhibited by individual‐site modifications of this study. Large nonadditivity may be correlated with global (quaternary) structure change.(5) Residue position vs. chemical nature. Functional response is solely dictated by structural location for a subset of the sites, but varies with side‐chain type at other sites. The current data base provides a unique framework for further analyses and modeling of fundamental issues in the structural chemistry of proteins and allosteric mechanisms. © 1992 Wiley‐Liss, Inc.
Limits on α‐helix prediction with neural network models
Authors: Hayward S. , Collins J. F. 
Published: May 2005

AbstractUsing a backpropagation neural network model we have found a limit for secondary structure prediction from local sequence. By including only sequences from whole α‐helix and non‐α‐helixstructures in our training and test sets—sequences spanning boundaries between these two structures were excluded—it was possible to investigate directly the relationship between sequence and structure for α‐helix. A group of non‐α‐helix sequences, that was disrupting overall prediction success, was indistinguishable to the network from α‐helix sequences. These sequences were found to occur at regions adjacent to the termini of α‐helices with statistical significance, suggesting that potentially longer α‐helices are disrupted by global constraints. Some of these regions spanned more than 20 residues. On these whole structure sequences, 10 residues in length, a comparatively high prediction success of 78% with a correlation coefficient of 0.52 was achieved. In addition, the structure of the input space, the distribution of β‐sheet in this space, and the effect of segment length were also investigated. © 1992 Wiley‐Liss, Inc.
Thermodynamic integration calculations of binding free energy difference for Gly‐169 mutation in subtilisin BPN′
Authors: Wang Cun Xin , Shi Yun Yu , Zhou Feng , Wang Lu 
Published: May 2005

AbstractThe binding free energy difference for the Gly‐169 → Ala‐169 (G169A) mutation in subtilisin BPN′ complexed with a tripeptide substrate analogue is explored using the thermodynamic integration approach. The structure of the mutant enzyme–substrate complex obtained from free energy simulation is in good agreement with experimental X‐ray refinement. The near perfect reversibility is obtained in the present work for ensuring the correctness of the free energy calculations. The results of the binding free energy difference are close to similar experimental data. © 1993 Wiley‐Liss, Inc.
Gaussian neighborhood: A new measure of accessibility for residues of protein molecules
Authors: Nauchitel Vladimir V. , Somorjai Rajmund L. 
Published: May 2005

AbstractWe introduce a new method for assessing the extent of residue exposure in proteins. For each atom of every residue a Gaussian‐weighted atomic surroundings value (the G‐neighborhood) is calculated. A normalized sum of G‐neighborhood values over all the atoms of a residue is complementary to conventional surface accessibility characteristics. The G‐0neighborhood value of a residue is a sensitive indicator of its location, strongly dependent on the 3D structure of a the protein. Correlations between secondary structures and patterns of G‐neighborhood values for six different protein molecules are discussed. Comparison of the distribution of hydrophobic and charged residues in the 3D structure for the alcohol‐soluble protein crambin and that of five water‐soluble proteins (cytochrome c, flavodoxin, myoglobin, rhodanese, and Bence–Jones protein) shows striking differences in their G‐neighborhood patterns. Contacts between the prosthetic group and the peptide portion of a protein as well as protein interdomain contacts and monomer–monomer contacts are characterized. © 1993 Wiley‐Liss, Inc.
A novel parameterization scheme for energy equations and its use to calculate the structure of protein molecules
Authors: Snow Mark E. 
Published: May 2005

AbstractA novel scheme for the parameterization of a type of “potential energy” function for protein molecules is introduced. The function is parameterized based on the known conformations of previously determined protein structures and their sequence similarity to a molecule whose conformation is to be calculated. Once parameterized, minima of the potential energy function can be located using a version of simulated annealing which has been previously shown to locate global and near‐global minima with the given functional form. As a test problem, the potential was parameterized based on the known structures of the rubredoxins from Desulfovibrio vulgaris, Desulfovibrio desulfuricans, and Clostridium pasteurianum, which vary from 45 to 54 amino acids in length, and the sequence alignments of these molecules with the rubredoxin sequence from Desulfovibrio gigas. Since the Desulfovibrio gigas rubredeoxin conformation has also been determined, it is possible to check the accuracy of the results. Ten simulated‐annealing runs from random starting conformations were performed. Seven of the 10 resultant conformations have an all‐Cα rms deviation from the crystallographically determined conformation of less than 1.7 Å. For five of the structures, the rms deviation is less than 0.8 Å. Four of the structures have conformations which are virtually identical to each other except for the position of the carboxy‐terminal residue. This is also the conformation which is achieved if the determined crystal structure is minimized with the same potential. The all‐Cα rms difference between the crystal and minimized crystal structures is 0.6 Å. It is further observed that the “energies” of the structures according to the potential function exhibit a strong correlation with rms deviation from the native structure. The conformations of the individual model structures and the computational aspects of the modeling procedure are discussed. © 1993 Wiley‐Liss, Inc.
Crystallization, preliminary X‐ray diffraction study, and crystal packing of a complex between anti‐Hen lysozyme antibody F9.13.7 and Guinea‐fowl lysozyme
Authors: Lescar Julien , Riottot Marie‐Madeleine , Souchon Hélène , Chitarra Véronique , Bentley Graham A. , Navaza Jorge , Alzari Pedro M. , Poljak Roberto J. 
Published: May 2005

AbstractThe complex formed between the Fab fragment of a murine monoclonal anti‐hen egg lysozyme antibody F9.13.7 and the het‐erologous antigen Guinea‐fowl egg lysozyme has been crystallized by the hanging drop technique. The crystals, which diffract X‐rays to 3 Å resolution, belong to the monoclinic space groupP21, witha= 83.7 Å,b= 195.5 Å,c= 50.2 Å, β = 108.5° and have two molecules of the complex in the asymmetric unit The three‐dimensional structure has been determined from a preliminary data set to 4 Å using molecular replacement techniques. The lysozyme–Fab complexes are arranged with their long molecular axes approximately parallel to the crystallo‐graphic unique axis. Fab F9.13.7 binds an anti‐genie determinant that partially overlaps the epitope recognized by antilysozyme antibody HyHEL10. © 1993 Wiley‐Liss, Inc.
Site‐specific proteolytic cleavage of Ku protein bound to DNA
Authors: Paillard Sophie , Strauss François 
Published: May 2005

AbstractKu protein, a relatively abundant nuclear protein associated with DNA of mammalian cells, is known to be a heterodimer with subunits of 85 and 72 kDa which binds in vitro to DNA ends and subsequently translocates along the molecule. The functional role played by this protein in the cell, however, remains to be elucidated. We have observed here that Ku protein, purified from cultured monkey cells, is the target of specific endoproteolysis in vitro, by which the 85 kDa subunit is cleaved at a precise site while the 72 kDa subunit remains intact. This cleavage releases an 18 kDa polypeptide and converts Ku protein into a heterodimer composed of the 72 kDa subunit associated with a 69 kDa fragment from the 85 kDa subunit. The proteolyzed form of Ku protein, denoted Ku′, has DNA binding properties similar to those of Ku protein. The proteolytic mechanism, which is inhibited by leupeptin and chymostatin, is extremely sensitive to ionic conditions, in particular to pH, being very active at pH 7.0 and completely inhibited at pH 8.0. In addition, cleavage occurs only when Ku protein is bound to DNA, not free in solution. We suggest that in vivo, such proteolysis might be necessary for Ku protein function at some stage of the cell cycle. © 1993 Wiley‐Liss, Inc.
Length distribution of CDRH3 in antibodies
Authors: Wu Tai Te , Johnson George , Kabat Elvin A. 
Published: May 2005

AbstractSequences of the third complementarity determining region of antibody heavy chains (CDRH3s) are listed according to their length. Human sequences vary from 2 to 26 amino acids residues, but less extensively in other species. When combined with the other five complementarity determining regions, this enormous length variation of CDRH3, together with amino acid substitutions in their sequences, can provide a very large number of antibody specificities and can influence the shape of antibody combining sites.©1993 Wiley‐Liss,Inc.
Computer modeling and folding of four‐helix bundles
Authors: Rey Antonio , Skolnick Jeffrey 
Published: May 2005

AbstractIn the context of simplified models of globular proteins, the requirements for the unique folding to a four‐helix bundle have been addressed through a new Monte Carlo procedure. In particular, the relative importance of secondary versus tertiary interactions in determining the nature of the folded structure is examined. Various cases spanning the extremes where tertiary interactions completely dominate to that where tertiary interactions are negligible have been explored. Not surprisingly, the folding to unique four‐helix bundles is found to depend on an adequate balance of the secondary and tertiary interactions. Moreover, because the simplified model is composed of spheres representing α‐carbons and side chains, the geometry of the latter being based on small real amino acids, the role played by the side chains, and the problems associated with packing and hard‐core repulsions, are considered. Also, possible folding intermediates and their relationship with the experimentally observed molten globule state are explored. From these studies, a general set of rules is extracted which should aid in the further design of more detailed protein models adequate to more fully investigate the protein folding problem. Finally, the relationship between our conclusions and experimental work with specifically designed sequences is briefly discussed. © 1993 Wiley‐Liss, Inc.