Biomedical subjects

T Blundell

Publications and source records attributed to T Blundell.

41 records · Page 3Linked to original sources

PubMed1975

X-ray analysis of glucagon and its relationship to receptor binding.

X-ray analysis of the pancreatic hormone glucagon shows that in crystals the polypeptide adopts a mainly helical conformation, which is stabilised by hydrophobic interactions between molecules related by threefold symmetry. A model is presented in which the glucagon molecule exists in dilute solutions as an equilibrium population of conformers with little retention of conformers with little retention of structure, and in which the helical conformation is stablised by hydrophobic interactions either as an oligomer or as a complex with the receptor.

Amino Acid Sequence↗

PubMedDate not supplied

Gene and protein structure of a beta-crystallin polypeptide in murine lens: relationship of exons and structural motifs.

A 23,000 molecular weight beta-crystallin (beta 23) of the murine eye lens is encoded in a 4.1 +/- 0.3-kilobase gene containing three introns. Each of the four exons seems to code for a separate structural motif of the protein, whose tertiary structure was predicted by an interactive computer graphics technique based on the crystallographic structure of bovine gamma II-crystallin. The first exon also encodes a hydrophobic N-terminal peptide resembling membrane anchor sequences of other proteins. Our results indicate structural homology among the beta- and gamma-crystallin polypeptides, and link gene structure with protein structure in this superfamily of lens proteins.

Amino Acid Sequence↗

PubMedDate not supplied

Three-dimensional structure, specificity and catalytic mechanism of renin.

Renin is an aspartyl proteinase that catalyses the first, and rate-limiting, step in the conversion of angiotensinogen to the hormone angiotensin II. The catalysis is highly specific, and plays an important physiological part in the regulation of blood pressure. For this reason inhibitors of renin are of potential value in the treatment of certain forms of hypertension. Although progress has been made in the design of inhibitors for clinical use by modification of angiotensinogen sequences, and as pepstatin analogues or with reduced peptide bonds, we have now provided the basis for a more rational approach by the use of interactive computer graphics techniques to build a three-dimensional model of renin. The model is based on the three-dimensional structure of endothia pepsin and the primary structure of mouse renin, which is very similar to that of the human enzyme. We show that renin may have a three-dimensional structure similar to that of other aspartyl proteinases.

Animals↗

PubMedDate not supplied

Solvent-induced distortions and the curvature of alpha-helices.

The alpha-helix defined in 1951 by Pauling et al. on the basis of model building and X-ray fibre diffraction data has 3.65 residues per turn (n) achieved with planar peptides, torsion angles of phi = -48 degrees and psi = -57 degrees and hydrogen bonds which are close to linear. Although X-ray analyses of proteins have confirmed the general correctness of the model for the helix, recent high resolution (1.7-1.0 A) diffraction studies have shown that the parameters described by Pauling et al. and later by Perutz and Arnott and Wonacott are not a good description of the alpha-helices in globular proteins, where the mean values of phi, psi are usually close to -63 degrees, -42 degrees. Here we show that these values arise as a mean of two significantly different classes in amphipathic helices depending on whether the peptide carbonyl oxygen is hydrogen bonded to a solvent or polar side-chain atom. The hydrogen bonds made by the hydrophilic carbonyls to the NH groups within helices are longer and less linear than those involving hydrophobic carbonyls. We also show that these effects are associated with a significant curvature of helices in globular proteins. For example, the alpha-helix in avian pancreatic peptide (aPP) has a radius of curvature of approximately 70 A. These results are of significance in the packing of helices in fibrous and globular proteins, in the calculation of their dipole moments, solvent accessibilities and internal energies, and in the theoretical estimation of spectroscopic properties such as circular dichroism and Raman scattering.

Pancreatic Polypeptide↗

PubMedDate not supplied

Myxococcus xanthus spore coat protein S may have a similar structure to vertebrate lens beta gamma-crystallins.

The Gram-negative bacterium Myxococcus xanthus has a complex life cycle during which large amounts of a protein of relative molecular mass (Mr) 19,000, known as protein S, are assembled into a spore surface coat by a process that specifically requires calcium ions. The gene for protein S has been cloned and the DNA sequence shows that the gene product is composed of four internally repeated homologous sequences, each 40 amino acids long. Although protein S resembles calmodulin both in its internally duplicated structure and its ability to bind calcium, it apparently has a beta-sheet secondary structure rather than the helix-loop-helix motifs that characterize the calmodulin family. We now show that protein S has a striking homology with the beta- and gamma-crystallins of the vertebrate eye lens which are beta-sheet proteins with internally duplicated structures. This implies that the beta- and gamma-crystallins evolved from already existing proteins, whose ancestors occurred in the prokaryotes. The biological function of protein S, as a closely packed, stable protein in a relatively dehydrated environment, has implications for the functions of crystallins, which are found closely packed in the lens fibre cells, where their stability is essential for maintenance of transparency.

Amino Acid Sequence↗