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D R Flower

Publications and source records attributed to D R Flower.

At least 19 recordsLinked to original sources
PubMed1999

PRINTS prepares for the new millennium.

PRINTS is a diagnostic collection of protein fingerprints. Fingerprints exploit groups of motifs to build characteristic family signatures, offering improved diagnostic reliability over single-motif approaches by virtue of the mutual context provided by motif neighbours. Around 1000 fingerprints have now been created and stored in PRINTS. The September 1998 release (version 20.0), encodes approximately 5700 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. The database is accessible via the DbBrowser Web Server at http://www.biochem.ucl.ac.uk/bsm/dbbrowser /. In addition to supporting its continued growth, recent enhancements to the resource include a BLAST server, and more efficient fingerprint search software, with improved statistics for estimating the reliability of retrieved matches. Current efforts are focused on the design of more automated methods for database maintenance; implementation of an object-relational schema for efficient data management; and integration with PROSITE, profiles, Pfam and ProDom, as part of the international InterPro project, which aims to unify protein pattern databases and offer improved tools for genome analysis.

Amino Acid Sequence↗
PubMed1998

The PRINTS protein fingerprint database in its fifth year.

PRINTS is a database of protein family 'fingerprints' offering a diagnostic resource for newly-determined sequences. By contrast with PROSITE, which uses single consensus expressions to characterise particular families, PRINTS exploits groups of motifs to build characteristic signatures. These signatures offer improved diagnostic reliability by virtue of the mutual context provided by motif neighbours. To date, 800 fingerprints have been constructed and stored in PRINTS. The current version, 17.0, encodes approximately 4500 motifs, covering a range of globular and membrane proteins, modular polypeptides, and so on. The database is accessible via the UCL Bioinformatics World Wide Web (WWW) Server at http://www. biochem.ucl.ac.uk/bsm/dbbrowser/ . We have recently enhanced the usefulness of PRINTS by making available new, intuitive search software. This allows both individual query sequence and bulk data submission, permitting easy analysis of single sequences or complete genomes. Preliminary results indicate that use of the PRINTS system is able to assign additional functions not found by other methods, and hence offers a useful adjunct to current genome analysis protocols.

Animals↗
PubMed1997

Bovine beta-lactoglobulin at 1.8 A resolution--still an enigmatic lipocalin.

BACKGROUND: beta-Lactoglobulin (beta-Lg) is the major whey protein in the milk of ruminants and many other mammals. Its function is not known, but it undergoes at least two pH-dependent conformational changes which may be important. Bovine beta-Lg crystallizes in several different lattices, and medium-resolution structures of orthorhombic lattice Y and trigonal lattice Z have been published. Triclinic lattice X and lattice Z crystals grow at pH values either side of the pH at which one of the pH-induced conformational changes occurs. A full understanding of the structure is needed to help explain both the conformational changes and the different denaturation behaviour of the genetic variants. RESULTS: We have redetermined the structure of beta-Lg lattice Z at 3.0 A resolution by multiple isomorphous replacement and have partially refined it (R factor = 24.8%). Using the dimer from this lattice Z structure as a search model, the triclinic crystal form grown at pH 6.5 (lattice X) has been solved by molecular replacement. Refinement of lattice X at 1.8 A resolution gave an R factor of 18.1%. The structure we have determined differs from previously published structures in several ways. CONCLUSIONS: Incorrect threading of the sequence in the published structures of beta-Lg affects four of the nine beta strands. The basic lipocalin fold of the polypeptide chain is unchanged, however. The relative orientation of the monomers in the beta-Lg dimer differs in the two lattices. On raising the pH, there is a rotation of approximately 5 degrees, which breaks a number of intersubunit hydrogen bonds. It is not yet clear, however, why the stability of the structure should depend so heavily upon the external loop around residue 64 or the beta strand with the free thiol, each of which shows genetic variation.

Amino Acid Sequence↗
PubMed1997

SERF: a program for accessible surface area calculations.

The program SERF has been designed to facilitate the greater use of accessible surface area calculations in the analysis of protein structure, including analysis of surface area changes on binding and complexation. For comparative purposes, the program implements a number of alternative methods for calculating surface areas, including those that approximate residues by single spheres. Algorithmic details, comparative performance, and the software implementation of SERF are discussed.

Algorithms↗
PubMed1997

ALTER: eclectic management of molecular structure data.

ALTER is a computer program written to facilitate easy conversion between different representations of molecular structure data. The program functions as a file converter, data generation engine, and through the creation of control or input files, as an interface to other programs. The main aspects of program function--the reading and writing of files; coordinate transformation; data reorganization: structure building; data abstraction, including the generation of a wide variety of topological indices and constitutional descriptors; and display--are described in appropriate detail.

Computer Graphics↗
PubMed1996

The lipocalin protein family: structure and function.

The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel beta-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily: the calycins. Members of the lipocalin family are characterized by several common molecular-recognition properties: the ability to bind a range of small hydrophobic molecules, binding to specific cell-surface receptors and the formation of complexes with soluble macromolecules. The varied biological functions of the lipocalins are mediated by one or more of these properties. In the past, the lipocalins have been classified as transport proteins; however, it is now clear that the lipocalins exhibit great functional diversity, with roles in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and, as carrier proteins, to act in the general clearance of endogenous and exogenous compounds.

Adjuvants, Immunologic↗
PubMed1996

P2T purinoceptor antagonists. A QSAR study of some 2-substituted ATP analogues.

FPL67085MX represents the first in a class of novel, highly potent and selective P2T purinoceptor antagonists which are inhibitors of adenosine diphosphate (ADP)-induced platelet aggregation in-vitro. In an early series of compounds we studied the effect of variation of the adenine 2-substituent on potency and derived quantitative structure-activity relationships (QSARs) between the properties of the molecules and their biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relative merits in terms of compound design. The model suggests that the receptor for these molecules has a narrow lipophilic cleft, which is occupied by the adenine 2-substituent.

Adenosine Triphosphate↗
PubMed1995

FOLD: integrated analysis and display of protein secondary structure.

FOLD, a computer program for the definition and analysis of protein secondary structure, is described. Algorithms implemented in the software are reviewed. These include methods for the identification of simple features such as hydrogen bonds, alpha helices, beta strands, beta bulges, and beta and psi turns. Techniques are also described for the definition and analysis of higher-order structures, such as beta hairpins, beta sheets and their topology, and beta barrels. In addition to considerable textual output the program supports visualization of protein secondary structure in either an atom-based display style or one reproducing the characteristics of a so-called ribbon drawing.

Computer Graphics↗
PubMed1994

The lipocalin protein family: a role in cell regulation.

The lipocalins, a large, diverse, but relatively poorly understood family of small extracellular proteins, are characterized by the ability to bind small hydrophobic molecules, such as retinol, and by their binding to specific cell surface receptors. These general properties suggest such proteins as appropriate transporters transferring biologically hazardous molecules in a safe and controlled manner between cells. Moreover, many lipocalins have been implicated in the regulation of cell homeostasis: apolipoprotein D, quiescience specific protein, purpurin, alpha-1-microglobulin, and NGAL. This combination of direct and indirect evidence suggests that the lipocalin protein family may be involved, in a quite general way, in the mediation of cell regulation and that many presently functionless family members might act in this way.

Amino Acid Sequence↗
PubMed1994

Beta-sheet topology. A new system of nomenclature.

The topology of a protein beta-sheet, the relationship between the sequential ordering of strands and their connectedness in space, is an important and well studied feature of protein structures. The prevalent nomenclature for describing beta-sheet topologies is based on following a path through the sequence order of strands and noting their separation in space. Although powerful, this approach can be usefully complemented by a notation based on following a path through the connectedness of neighbouring strands and noting sequence separation. This leads in turn to a short hand expression of sheet topology, based on a method for describing the covalent structure of small molecules, which is able to express concisely the complex non-linear topological relationships of beta-sheets, including bifurcations and closed structures, in a clear and natural manner. Using this novel system of notation it is possible to follow simultaneously the sequence and hydrogen bonded connectedness of strands within the topology of a sheet.

Hydrogen Bonding↗
PubMed1994

Automating the identification and analysis of protein beta-barrels.

beta-Barrels are widespread and well-studied features of a great many protein structures. In this paper an unsupervised method for the detection of beta-barrels is developed based on techniques from graph theory. The hydrogen bonded connectivity of beta-sheets is derived using standard pattern recognition techniques and expressed as a graph. Barrels correspond to topological rings in these connectivity graphs and can thus be identified using ring perception algorithms. Following from this, the characteristic topological structure of a barrel can be expressed using a novel form of reduced nomenclature that counts sequence separations between successive members of the ring set. These techniques are tested by applying them to the detection of barrels in a non-redundant subset of the Brookhaven database. Results indicate that topological rings do seem to correspond uniquely to beta-barrels and that the technique, as implemented, finds the majority of barrels present in the dataset.

Algorithms↗
PubMed1993

Structural relationship of streptavidin to the calycin protein superfamily.

Streptavidin is a binding protein, from the bacteria Streptomyces avidinii, with remarkable affinity for the vitamin biotin. The lipocalins and the fatty acid-binding proteins (FABPs), are two other protein families which also act by binding small hydrophobic molecules. Within a similar overall folding pattern (a beta-barrel with a repeated +1 topology), large parts of the lipocalin, FABP, and streptavidin molecules can be structurally equivalenced. The first structurally conserved region within the three-dimensional alignment, or common core, characteristic of the three groups corresponds to an unusual structural feature (a short 3(10) helix leading into a beta-strand, the first of the barrel), conserved in both its conformation and its location within their folds, which also displays characteristic sequence conservation. These similarities of structure and sequence suggest that all three families form part of a larger group: the calycin structural superfamily.

Amino Acid Sequence↗
PubMed1993

Structure and sequence relationships in the lipocalins and related proteins.

The lipocalins and fatty acid-binding proteins (FABPs) are two recently identified protein families that both function by binding small hydrophobic molecules. We have sought to clarify relationships within and between these two groups through an analysis of both structure and sequence. Within a similar overall folding pattern, we find large parts of the lipocalin and FABP structures to be quantitatively equivalent. The three largest structurally conserved regions within the lipocalin common core correspond to characteristic sequence motifs that we have used to determine the constitution of this family using an iterative sequence analysis procedure. This afforded a new interpretation of the family, which highlighted the difficulties of determining a comprehensive and coherent classification of the lipocalins. The first of the three conserved sequence motifs is also common to the FABPs and corresponds to a conserved structural element characteristic of both families. Similarities of structure and sequence within the two families suggests that they form part of a larger "structural superfamily"; we have christened this overall group the calycins to reflect the cup-shaped structure of its members.

Alpha-Globulins↗
PubMed1992

Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography.

The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.

Alpha-Globulins↗