PubMed HealthSearch

Biomedical subjects

A Kajihara

Publications and source records attributed to A Kajihara.

13 recordsLinked to original sources

Three-dimensional model of the human PAF receptor.

The amino acid sequence analysis of the human platelet-activating factor (PAF) receptor showed that residues thought to be important structurally and functionally were well conserved. This suggested similarities of the three-dimensional structure (3D structure) between the human PAF receptor and other receptors that couple to guanine nucleotide binding (G) proteins. Thus, a three-dimensional model of this receptor was constructed using the 3D structure of bacteriorhodopsin as the reference protein, by means of the BIOCES[E] computer-modeling system. This model has seven alpha-helical transmembrane segments which form a central core and an S-S bond between the second and third extracellular loops. The distance of the S-S bond is about 2 A, which is thought to be reasonable. In the transmembrane domain, the side chains of Asp-63, Asn-285 and Asp-289 became oriented toward the central core and form a negatively charged site. This receptor model suggests that the positively charged choline moiety of PAF is attracted to this negatively charged site by electrostatic forces and that PAF may induce conformational changes in the receptor, leading to G-protein activation.

Amino Acid Sequence

Protein modelling using a chimera reference protein derived from exons.

Bovine pancreatic beta-trypsin (PDB ID-code: 1TPO) which is registered in the Brookhaven Protein Data Bank (PDB) consists of four exons. The results of homology searches for each exon in the PDB showed that homologous proteins were tonin (PDB ID-code: 1TON), rat mast cell protease (PDB ID-code: 3RP2__A), kallikrein A (PDB ID-code: 2PKA__B) and kallikrein A (2PKA__B) respectively. Thus, for the three-dimensional structure prediction of 1TPO, a chimera protein was constructed from the three proteins mentioned above and the 3-D structure prediction was performed using this chimera reference protein. The modelled structure of 1TPO was energetically optimized by molecular mechanics and molecular dynamics simulation and was compared with its X-ray crystal structure registered in the PDB. The root mean square deviations (r.m.s.d.) of main chain atoms and the neighbouring active site (5 A sphere from His57, Asp102 and Ser195) between the modelled structure and the X-ray structure were 1.66 and 0.94 A respectively. Porcine pancreatic elastase (PDB ID-code: 3EST) which is registered in the PDB was used as the reference protein and the modelled structure from 3EST was also compared with the X-ray data. The r.m.s.d. of main chain atoms and that of the active site were 2.14 and 1.18 A respectively. These results clearly support the propriety of this method using the chimera reference protein.

Algorithms

Effect of acute exposure to cold on the levels of corticosterone and pituitary hormones in plasma collected from free conscious cannulated rats.

To investigate the initial response of the pituitary and adrenal cortex functionings of rats acutely exposed to cold, we developed a technique for cannulation which allowed sequential blood collection from conscious and freed rats. Two cannulae were inserted, one into the carotid artery used for collection and the other into the femoral vein for blood transfusion to keep the blood volume constant. Significant increases in plasma corticosterone and thyrotropin were evoked within 15 min after exposure. While plasma growth hormone (GH) slightly decreased, and the prolactin level tended to fall by 1 hr after cold exposure but the difference was not significant as compared with control values.

Animals