bluuebunny/crossref_metadata_2025_split huggingface dataset:
A structural assessment of the apo[a] protein of human lipoprotein[a]
Authors: Guevara Juan , Knapp Roger D. , Honda Sandra , Northup S. Robert , Morrisett Joel D. 
Published: May 2005

AbstractApolipoprotein[a], the highly glycosylated, hydrophilic apoprotein of lipoprotein[a] (Lp[a]), is generally considered to be a multimeric homologue of plasminogen, and to exhibit atherogenic/thrombogenic properties. The cDNA‐inferred amino acid sequence of apo[a] indicates that apo[a], like plasminogen and some zymogens, is composed of a kringle domain and a serine protease domain. To gain insight into possible positive functions of Lp[a], we have examined the apo[a] primary structure by comparing its sequence with those of other proteins involved in coagulation and fibrinolysis, and its secondary structure by using a combination of structure prediction algorithms. The kringle domain encompasses 11 distinct types of repeating units, 9 of which contain 114 residues. These units, called kringles, are similar but not identical to each other or to PGK4. Each apo[a] kringle type was compared with kringles which have been shown to bind lysine and fibrin, and with bovine prothrombin kringle 1. Apo[a] kringles are linked by serine/threonine‐ and proline‐rich stretches similar to regions in immunoglobulins, adhesion molecules, glycoprotein Ib‐α subunit, and kininogen. In comparing the protease domains of apo[a] and plasmin, apo[a] contains a region between positions 4470 and 4492 where 8 substitutions, 9 deletions, and 1 insertion are apparent. Our analysis suggests that apo[a] kringle‐type 10 has a high probability of binding to lysine in the same way as PGK4. In the only human apo[a] polymorph sequenced to date, position 4308 is occupied by serine, whereas the homologous position in plasmin is occupied by arginine and is an important site for proteolytic cleavage and activation. An alternative site for the proteolytic activation of human apo[a] is proposed.
Functional significance of conserved amino acid residues
Authors: Poteete Anthony R. , Rennell Dale , Bouvier Suzanne E. 
Published: May 2005

AbstractA systematic study of single amino acid substitutions in bacteriophage T4 lysozyme permitted a test of the concept that conserved amino acid residues are more functionally important than nonconserved residues. Substitutions of amino acid residues that are conserved among five bacteriophage‐encoded lysozymes were found to lead more frequently to loss of function than substitutions of nonconserved residues. Of 163 residues tested, only 74 (45%) are sensitive to at least one substitution; however, all 14 residues that are fully conserved are sensitive to substitutions. © 1992 Wiley‐Liss, Inc.
Monte Carlo docking of oligopeptides to proteins
Authors: Caflisch Amedeo , Niederer Peter , Anliker Max 
Published: May 2005

AbstractA new two‐step procedure has been developed for the docking of flexible oligopeptide chains of unkown conformation to static proteins ofknown structure. In the first step positions and conformations are sampled and the association energy, minimized starting from an approximate preselected docking position. The resulting conformations are further optimized in the second step by a Metropolis Monte Carlo minimization, which optimizes each of these structures. The method has been tested on the HIV‐1 aspartic proteinase complex with an inhibitor, whose crystallographic structure is known at 2.3 Å resolution. Furthermore, the application of this method to the docking of the hendecapeptide 58–68 of the influenza A virus matrix protein to the HLA‐A2 molecule produced results which are in agreement with experimental observations in identifying side chains critical for T cell recognition and residues responsible of MHC protein binding. © 1992 Wiley‐Liss, Inc.
Molecular dynamics characterization of the active cavity of carboxypeptidase A and some of its inhibitor adducts
Authors: Banci Lucia , Schröder Stefan , Kollman Peter A. 
Published: May 2005

AbstractMolecular dynamics (MD) calculations have been performed on carboxypeptidase A and on its adducts with inhibitors, such as d‐phenylalanine (dPhe) and acetate. The catalytically essential zinc ion present in the protein was explicitly included in all the simulations. The simulation was carried out over a sphere of 15 Å centered on the zinc ion. The crystallographic water molecules were explicitly taken into account; then the protein was solvated with a 18 Å sphere of water molecules. MD calculations were carried out for 45–60 ps. There is no large deviation from the available X‐ray structures of native and the dPhe adduct for the MD stuctures. Average MD structures were calculated starting from the X‐ray structure of the dPhe adduct, and, from a structure obtained by docking the inhibitor in the native structure. Comparison between these two structures and with that of the native protein shows that some of the key variations produced by inhibitor binding are reproduced by MD calculations. Addition of acetate induces structural changes relevant for the understanding of the interaction network in the active cavity. The structural variations induced by different inhibitors are examined. The effects of these interactions on the catalytic mechanism and on the binding of substrate are discussed. © 1992 Wiley‐Liss, Inc.
The refined crystal structure of Pseudomonas putida lipoamide dehydrogenase complexed with NAD+ at 2.45 Å resolution
Authors: Mattevi Andrea , Obmolova Galya , Sokatch John R. , Betzel Christian , Hol Wim G. J. 
Published: May 2005

AbstractThe three‐dimensional structure of one of the three lipoamide dehydroge‐nases occurring in Pseudomonas putida, LipDH Val, has been determined at 2.45 Å resolution. The orthorhombic crystals, grown in the presence of 20 mM NAD+, contain 458 residues per asymmetric unit. A crystallographic 2‐fold axis generates the dimer which is observed in solution. The final crystallographic R‐factor is 21.8% for 18,216 unique reflections and a model consisting of 3,452 protein atoms, 189 solvent molecules and 44 NAD+ atoms, while the overall B‐factor is unusually high; 47 Å2.The structure of LipDH Val reveals the conformation of the C‐terminal residues which fold “back” into the putative lipoamide binding region. The C‐terminus has been proven to be important for activity by site‐directed mutagene‐sis. However, the distance of the C‐terminus to the catalytically essential residues is surprisingly large, over 6 Å, and the precise role of the C‐terminus still needs to be elucidated.In this crystal form LipDH Val contains one NAD+ molecule per subunit. Its adenine‐ribose moiety occupies an analogous position as in the structure of glutathione reductase. However, the nicotinamide‐ribose moiety is far removed from its expected position near the isoallox‐azine ring and points into solution.Comparison of LipDH Val with Azotobacter vinelandii lipoamide dehydrogenase yields an rms difference of 1.6 Å for 440 well defined Cα atoms per subunit. Comparing LipDH Val with glutathione reductase shows large differences in the tertiary and quaternary structure of the two enzymes. For instance, the two subunits in the dimer are shifted by 6 Å with respect to each other. So, LipDH Val confirms the surprising differences in molecular architecture between glutathione reductase and lipoamide dehydrogenase, which were already observed in Azotobacter vinelandii LipDH. This is the more remarkable since the active sites are located at the subunit interface and are virtually identical in all three enzymes. © 1992 Wiley‐Liss, Inc.
A systematic search for protein signature sequences
Authors: Sheridan Robert P. , Venkataraghavan R. 
Published: May 2005

AbstractSignature sequences are contiguous patterns of amino acis 10‐50 resiues long that are associated with a particular structure or function in proteins. These may be of three types (by our nomenclature): superfamily signatures, remnant homologies, and motifs. We have performed a systematic search through a database of protein sequences to automatically and preferentially find remnant homologies and motifs. This was accomplished in three steps:

We generated a nonredundant sequence database.
We used BLAST3 (Altschul and Lipman, Proc. Natl. Acad. Sci. U.S.A. 87:5509–‐5513, 1990) to generate local pairwise and triplet sequence alignments for every protein in the database vs. every other.
We selected “interesting” alignments and grouped them into clusters. We find that most of the clusters contain segments from proteins which share a common structure or function. Many of them correspond to signatures previously noted in the literature. We discuss three previously recognized motifs in detail (FAD/NAD‐binding, ATP/GTP‐binding, and cytochrome b5‐like domains) to demonstrate how the alignments generated by our procedure are consistent with previous work and make structural and functional sense. We also discuss two signatures (for N‐acetyltransferases and glycerol‐phosphate binding) which to our knowledge have not been previously recognized. © 1992 Wiley‐Liss, Inc.
Fast structure alignment for protein databank searching
Authors: Orengo Christine A. , Brown Nigel P. , Taylor William R. 
Published: May 2005

AbstractA fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming.Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage.It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein Structure. © 1992 Wiley‐Liss, Inc.
Functional roles of amino acid residues involved in forming the α–helix‐turn–α–helix operator DNA binding motif of tet represser from Tn10
Authors: Baumeister Ralf , Müller Gerhard , Hecht Brigitte , Hillen Wolfgang 
Published: May 2005

AbstractThe Tn10derived Tet represser contains an amino acid segment with high homology to the α‐helix–turn–α‐helix motif (HTH) of other DNA binding proteins. The five most conserved amino acids in HTH are probably involved in structural formation of the motif. Their functional role was probed by saturation mutagenesis yielding 95 single amino acid replacement mutants of Tet repressor. Their binding efficiencies to tet operator were quantitatively determined in vivo. All functional mutants contain amino acid substitutions consistent with their proposed role in a HTH. In particular, only the two smallest amino acids (serine, glycine) can substitute a conserved alanine in the proposed first α‐helix without loss of activity. The last position of the first α‐helix, the second position in the turn, and the fourth position in the second α‐helix require mostly hydrophobic residues. The proposed C‐terminus of the first α‐helix is supported by a more active asparagine compared to glutamine replacement mutant of the wt leucine residue. The turn is located close to the protein surface as indicated by functional lysine and arginine replacements for valine. A glycine residue at the first position in the turn can be replaced by any amino acid yielding mutants with at least residual tet operator affinity. A structural model of the HTH of Tet repressor is presented. © 1992 Wiley‐Liss, Inc.
Structural principles for the propeller assembly of β‐sheets: The preference for seven‐fold symmetry
Authors: Murzin Alexey G. , Murzin Alexey G. 
Published: May 2005

AbstractTwisted β‐sheets, packed face to face, may be arranged in circular formation like blades of a propeller or turbine. This β‐pro‐peller fold has been found in three proteins: that in neuraminidase consists of six β‐sheets while those in methylamine dehydrogenase and galactose oxidase are composed of seven β‐sheets. A model for multisheet packing in the β‐propeller fold is proposed. This model gives both geometrical parameters of the β‐propellers composed of different numbers of sheets and patterns of residue packing at their sheet‐to‐sheet interfaces. All the known β‐propeller structures have been analyzed, and the observed geometries and residue packing are found to be in good agreement with those predicted by models. It is shown that unusual seven‐fold symmetry is preferable to six‐ or eight‐fold symmetry for propeller‐like multisheet assembly. According to the model, a six β‐sheet propeller has to have predominantly small residues in the β‐strands closed to its sixfold axis, but no strong sequence constraints are necessary for a seven‐fold β‐propeller. © 1992 Wiley‐Liss, Inc.
Fast and simple monte carlo algorithm for side chain optimization in proteins: Application to model building by homology
Authors: Holm Lisa , Sander Chris 
Published: May 2005

AbstractAn unknown protein structure can be predicted with fair accuracy once an evolutionary connection at the sequence level has been made to a protein of known 3‐D structure. In model building by homology, one typically starts with a backbone framework, rebuilds new loop regions, and replaces nonconserved side chains. Here, we use an extremely efficient Monte Carlo algorithm in rotamer space with simulated annealing and simple potential energy functions to optimize the packing of side chains on given backbone models. Optimized models are generated within minutes on a workstation, with reasonable accuracy (average of 81% side chain χ1 dihedral angles correct in the cores of proteins determined at better than 2.5 Å resolution). As expected, the quality of the models decreases with decreasing accuracy of backbone coordinates. If the backbone was taken from a homologous rather than the same protein, about 70% side chain X1 angles were modeled correctly in the core in a case of strong homology and about 60% in a case of medium homology. The algorithm can be used in automated, fast, and reproducible model building by homology. © 1992 Wiley‐Liss, Inc.
Three‐dimensional structure of the quinoprotein methylamine dehydrogenase from Paracoccus denitrificans determined by molecular replacement at 2.8 Å resolution
Authors: Chen Longyin , Mathews F. Scott , Davidson Victor L. , Huizinga Eric G. , Vellieux Frederic M. D. , Hol Wim G. J. 
Published: May 2005

AbstractThe three‐dimensional structure of the quinoprotein methylamine dehydrogenase from Paracoccus denitrificans (PD‐MADH) has been determined at 2.8 Å resolution by the molecular replacement method combined with map averaging procedures, using data collected from an area detector. The structure of methylamine dehydrogenase from Thio‐bacillus versutus, which contains an “X‐ray” sequence, was used as the starting search model. MADH consists of 2 heavy (H) and 2 light (L) subunits related by a molecular 2‐fold axis. The H subunit is folded into seven four‐stranded β‐segments, forming a disk‐shaped structure, arranged with pseudo‐7‐fold symmetry. A 31‐residue elongated tail exists at the N‐terminus of the H subunit in MADH from T. versutus but is partially digested in this crystal form of MADH from P. denitrificans, leaving the H subunit about 18 residues shorter. Each L subunit contains 127 residues arranged into 10 β‐strands connected by turns. The active site of the enzyme is located in the L subunit and is accessible via a hydrophobic channel between the H and L subunits. The redox cofactor of MADH, tryptophan tryptophylquinone is highly unusual. It is formed from two co‐valently linked tryptophan side chains at positions 57 and 107 of the L subunit, one of which contains an orthoquinone. © 1992 Wiley‐Liss, Inc.
Structure of a rhombohedral R6 insulin/phenol complex
Authors: Smith G. David , Dodson Guy G. 
Published: May 2005

AbstractHexameric insulin has been crystallized from different conditions ina variety of crystalline modifications. In the presence of ∼1%phenol and at a pH of 8.5, a new rhom‐bohedral form is produced, space group R3, a = 79.92 Åand c = 40.39 Å, in whichthe asymmetric unit consists of a dimer. The structur has been solved and refined, using data between 8.0 and 2.5 Å resolution, to a residual of0.157. The two monomers in the asymmetric unit have nearly identical R conformations, that is, residues Bl through B8 are α‐helical, producing a continuous α‐helix from Bl through B19. A phenol molecule is hydrogen bonded to the carbonyl oxygen of A6 Cys of each monomer. Small differences in conformation and the final (2Fo‐Fc) and difference electron density maps suggest that an additional phenol molecule is coordinated to one of the two zinc ions.
Pitch diversity in α‐helical coiled coils
Authors: Seo John , Cohen Carolyn 
Published: May 2005

AbstractTwo complementary methods for measuring local pitch based on heptad position in α‐helical coiled coils are described and applied to six crystal structures. The results reveal a diversity of pitch values: two‐stranded coiled coils appear to have pitch values near 150 Å the values for three‐ and four‐stranded coiled coils range closer to 200 Å. The methods also provide a rapid and sensitive gauge of local coiled‐coil conformation. Polar or charged residues in the apolar interface between coiled‐coil helices markedly affect local pitch values, suggesting a connection between pitch uniformity and coiled‐coil stability. Moreover, the identification of a skip residue (heptad frame shift) in the hemaglutinin glycoprotein of influenza virus (HA) allows interpretation of local pitch changes. These results on relatively short coiled‐coil structures have relevance for the much longer fibrous proteins (many of which have skip residues) whose detailed structures are not yet established. We also show that local pitch values from molecular dynamics predictions of the GCN4 leucine zipper are in striking agreement with the high‐resolution crystal structure—a result not readily discerned by direct comparison of atomic coordinates. Taken together, these methods reveal specific aspects of coiled‐coil structure which may escape detection by global analyses of pitch. © 1993 Wiley‐Liss, Inc.
βVI Turns in peptides and proteins: A model peptide mimicry
Authors: Müller Gerhard , Gurrath Marion , Kurz Michael , Kessler Horst 
Published: May 2005

AbstractTo investigate the role of proline in defining β turn conformations within cyclic hexa‐ and pentapeptides we synthesized and determined the conformations of a series of L‐ and D‐proline‐containing peptides by means of 2D NMR spectroscopy and restrained molecular dynamics simulations. Due to cis/trans isomerism the L‐proline peptides adopt at least two different conformations that are analyzed and compared to the structures of the corresponding D‐proline peptides. The cis conformations of the compounds cyclo(‐Pro‐Ala‐Ala‐Pro‐Ala‐Ala‐), cyclo(‐Arg‐Gly‐Asp‐Phe‐Pro‐Gly‐), cyclo(‐Arg‐Gly‐Asp‐Phe‐Pro‐Ala‐), cyclo(‐Pro‐Ala‐Ala‐Ala‐Ala‐‐), and cyclo(‐Pro‐Ala‐Pro‐Ala‐Ala‐) form uncommon βVI turns that mimic the turn geometries found in crystallographically refined protein structures at such a detailed level that even preferred side chain orientations are reproduced. The ratios of the cis/trans isomers are analyzed in terms of the steric demand of the proline‐following residue. The conformational details derived from this study illustrate the importance of the examination of small model compounds derived from protein loop regions, especially if bioactive recognition sequences, such as RGD (Arg‐Gly‐Asp), are incorporated. © 1993 Wiley‐Liss, Inc.
A novel computer modeling approach to the structures of small bioactive peptides: The structure of gonadotropin releasing hormone
Authors: Gupta Hema M. , Talwar Gursaran P. , Salunke Dinakar M. 
Published: May 2005

AbstractA novel computer modeling approach suitable for the structure analysis of small bioactive peptides has been developed. This approach involves identification of conformational patterns in protein structure data bank based on the sequence homology with the bioactive peptide. The models built on the basis of this homology and having common conformational patterns are analyzed under the structural constraints derived from the activity data of various synthetic analogs of the peptide. Application of this procedure to the gonadotropin releasing hormone (GnRH) resulted in a library of possible structures for GnRH, 9 among which shared a common β‐turn. Further analysis of the structures containing the β‐turn motif, in the context of the structure–activity data, led to a model for the active conformation of GnRH. The topology of the putative receptor binding site of the hormone is defined by a contiguous surface formed through an appropriate juxtaposition of the N‐terminal pGlu1 the guanidyl group of Arg8, aromatic side chain of Trp3, and the Gly10‐NH2 at the C‐terminal end. ©Wiley‐Liss, Inc.
An empirical energy function for threading protein sequence through the folding motif
Authors: Bryant Stephen H. , Lawrence Charles E. 
Published: May 2005

AbstractIn this paper we present a new residue contact potantial derived by statistical analysis of protein crystal structures. This gives mean hydrophobic and pairwise contact energies as a function of residue type and distance interval. To test the accuracy of this potential we generate model structures by “threading” different sequences through backbone folding motifs found in the structural data base. We find that conformational energies calculated by summing contact potentials show perfect specificity in matching the correct sequences with each globular folding motif in a 161‐protcin data set. They also identify correct models with the core folding motifs of heme‐rythrin and immunoglobulin McPC603 V1‐do‐ main, among millions of alternatives possible when we align subsequences with α‐helices and β‐strands, and allow for variation in the lengths of intervening loops. We suggest that contact potentials reflect important constraints on nonbonded interaction in native proteins, and that “threading” may be useful for structure prediction by recognition of folding motif. © 1993 Wiley‐Liss, Inc.