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Biomedical subjects

V B Cockcroft

Publications and source records attributed to V B Cockcroft.

8 recordsLinked to original sources
PubMed1993

Homologies and disparities of glutamate receptors: a critical analysis.

Based on analysis of aligned amino acid sequences the following statements are made: (i) There is evolutionary homology between the N-terminal extracellular region of ionotropic Glutamate receptors/Kainate Binding Proteins and a family of procaryote amino acid binding proteins. (ii) Homology of the N-terminal extracellular domain of the metabotropic glutamate receptors with a family of receptors with a guanylate cyclase intracellular domain appears to be valid. (iii) There is no evidence for homology between the N-terminal extracellular domain of the nicotinic Acetylcholine, GABA, Glycine and 5HT3 receptors and that of the ionotropic Glutamate receptors/Kainate Binding proteins. (iv) The proposal of homology for the N-terminal extracellular domain of metabotropic Glutamate receptors and that of ionotropic Glutamate receptors does not appear to hold.

Animals↗
PubMed1993

CEDIT: a C interface and macro facility for protein sequence alignment editing in colour with Microsoft Word 5.0 for PCs.

CEDIT, a C interface and macro facility that provides for the colour editing of protein sequence alignments (up to 2000 sequences, 5000 residues each) using Microsoft Word 5.0 for PCs is presented. CEDIT uses the ability of MS-Word 5.0 to display letters with the desired colour to easily identify conservative homologies across the sequences. A glossary file with useful macros for the sequence editing is provided, along with several utilities programs for error checking, estimating sequence similarities and homology significance. CEDIT has a menu interface and a context sensitive help.

Amino Acid Sequence↗
PubMed1992

BIOSITE: a program for the interactive comparison of aligned homologous protein sequences.

A program, BIOSITE, providing for the interactive visual comparison of aligned homologous amino-acid sequences is presented, including an example of its application. The program allows for two types of comparison sequence to be generated: an 'identity' sequence and a 'difference' sequence. These may be used on subsets of sequences and in further comparisons to identify candidate sites involved in a distinct functional property. The program should prove a useful tool for biologists engaged in understanding sequence--function relationships.

Amino Acid Sequence↗
PubMed1991

Relative-residue surface-accessibility patterns reveal myoglobin and catalase similarity.

A novel sliding-window search method using relative-residue surface-accessibility patterns identified extensive, but unsuspected, structural similarity over a 3-helix region in the C-terminus of the evolutionarily unrelated proteins sperm-whale myoglobin and beef liver catalase. This clear example of structural similarity between non-homologous proteins highlights the importance of relative-residue surface-accessibility patterns in understanding the local folded structure in proteins.

Amino Acid Sequence↗
PubMed1990

Methyllycaconitine: a selective probe for neuronal alpha-bungarotoxin binding sites.

The ability of methyllycaconitine (MLA) to inhibit the binding of [125I]alpha-bungarotoxin to rat brain membranes, frog and human muscle extracts and the human muscle cell line TE671 has been measured. MLA showed a markedly higher affinity for the rat brain site (Ki 1.4 x 10(-9) M) than for the muscle receptors (Ki 10(-5)-10(-6) M). Structure modelling techniques were used to fit the structure of MLA to a nicotinic pharmacophore model. MLA is the first low molecular weight ligand to be shown to discriminate between muscle nicotinic receptors and their alpha-bungarotoxin-binding counterpart in the brain, and as such may be a useful structural probe for pursuing the structural and functional properties of the neuronal protein.

Aconitine↗
PubMed1990

Modeling of agonist binding to the ligand-gated ion channel superfamily of receptors.

A generalized model is presented of agonist binding to ligand-gated ion channels (LGICs). Broad similarity in the structure of agonists suggests that the binding sites of LGICs may have evolved from a protobinding site. Aligned sequence data identified as a candidate for such a site a highly conserved 15 residue stretch of primary structure in the N-terminal extracellular region of all known LGIC subunits. We modeled this subregion, termed the cys-loop, as a rigid, amphiphilic beta-hairpin and propose that it may form a major determinant of a conserved structural binding cleft. In the model of the binding complex (1) an invariant aspartate residue at position 11 of the cys-loop is the anionic site interacting with the positively charged amine group of agonists, (2) a local dipole within the pi-electron system of agonists is favorably oriented in the electrostatic field of the invariant aspartate, (3) the epsilon ring-proton of a conserved aromatic residue at the turn of the cys-loop interacts orthogonally with the agonist pi-electron density at its electronegative center, and (4) selective recognition is partly a result of the type of amino acid residue at position 6 of the cys-loop. Additionally, formation of a hydrogen bond between the electronegative atom of the pi-electron system of agonist and a complementary group in the receptor may be important in the high-affinity binding of agonists.

Amino Acid Sequence↗
PubMed1990

Modelling of binding sites of the nicotinic acetylcholine receptor and their relation to models of the whole receptor.

Models for the acetylcholine (ACh)-binding site of the nicotinic acetylcholine receptor (nAChR) are proposed. These models have been developed by using the concept of the ligand-gated ion-channel (LGIC) superfamily of receptors that have evolved from a common ancestor. An initial component of the binding site was identified as a highly conserved 15-residue stretch of primary structure in the N-terminal extracellular region of all known LGIC subunits, based on aligned sequence data of LGICs. This subregion, termed the Cys-loop, was modelled as an amphiphilic beta-hairpin and we propose that it forms a major determinant of the binding cleft for agonists. This initial, partial binding-site model has been extended to include residues biochemically identified as spatially adjacent to the binding cleft. A recently developed technique for rapidly scanning the known protein structural database for 'non-homologous similarity' using just sequence information identified the known structure of the enzyme pyrophosphatase (PPase) as a candidate scaffold for the N-terminal domain of the nAChR. This similarity was investigated further using sequence alignments. A framework model of the full N-terminal domain in which the position of the Cys-loop and other binding-site determinants, as well as the main immunogenic region (MIR), have been mapped on to the PPase structure.

Amino Acid Sequence↗