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D R Flower

Publications and source records attributed to D R Flower.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Crystallization and initial X-ray analysis of the C2-subunit of crustacyanin.

Crystals of the C2-subunit of crustacyanin have been grown from solutions containing ammonium sulphate and 2-methyl-2,4-pentanediol as co-precipitants. The crystals belong to space group P2(1)2(1)2(1) (a = 42.0 A, b = 80.9 A, c = 110.8 A) with two subunits per asymmetric unit and diffract beyond 2.2 A resolution.

Carrier Proteins↗
PubMed1991

Mouse oncogene protein 24p3 is a member of the lipocalin protein family.

Rigorous new methods of protein sequence analysis have been applied to the lipocalins, a diverse family of ligand binding proteins. Using three conserved sequence motifs to search for similar patterns in a large sequence database, the size and composition of this protein family have been defined in an automatic and objective way. It has allowed the identification of an existing sequence, mouse 24p3 protein, as a lipocalin and the possible rejection of other putative members from this protein family. On the basis of this newly discovered homology, a possible function for mouse 24p3 protein is proposed.

Acute-Phase Proteins↗
PubMed1991

Improved ribbon-drawing programs.

We describe significant improvements to RIBBON (a program system that produces schematic pictures of proteins) that extend its capabilities and simplify its use. Enhanced features include the drawing of ligands as an integral part of the picture and in a variety of styles, greater control of the displayed image, and a much improved user-interface.

Computer Simulation↗
PubMedDate not supplied

Multiple molecular recognition properties of the lipocalin protein family.

The lipocalins, a diverse family of small extracellular ligand binding proteins, display a remarkable range of different molecular recognition properties. While their binding of small hydrophobic molecules, and to a lesser extent their binding to cell surface receptors, is well known, it is shown here that formation of macromolecular complexes is also a common feature of this family. Analysis of known crystallographic structures reveals that the lipocalins possess a conserved common structure: an antiparallel beta-barrel with a repeated +1 topology. Comparisons show that within this overall similarity the structure of individual proteins is specifically adapted to bind their particular ligands, forming a binding site from an internal cavity (within the barrel) and/or an external loop scaffold, which gives rise to different binding modes that reflects the need to accommodate ligands of different shape, size, and chemical structure. The architecture of the lipocalin fold suggests that both the ends and sides of this barrel are topologically distinct, differences also apparent in analyses of structural and sequence variation within the family. These differences can be linked to experimental evidence suggesting a possible functional dichotomy between the two ends of the lipocalin fold. The structurally invariant end of the molecule may be implicated in general binding to common cell surface receptors, while the more variable end is adapted to the specialised tasks of binding small ligands and forming macromolecular complexes via an exposed binding surface.

Amino Acid Sequence↗