Biomedical subjects

Atsushi Kasuya

Publications and source records attributed to Atsushi Kasuya.

5 recordsLinked to original sources

PubMed2005

Structural elucidation of A-74528, an inhibitor for 2',5'-phosphodiesterase isolated from Streptomyces sp.

A-74528 (1) is a metabolite of Streptomyces sp. discovered in the screening for 2',5'-oligoadenylate phosphodiesterase inhibitors. The planar structure of 1 was mainly elucidated by NMR techniques including natural abundance INADEQUATE, and the relative configuration and the conformation were elucidated by the analyses of NOEs and assessment of dihedral angles predicted by QUANTA/CHARMm computations and coupling constants. It was proved that 1 is a highly fused polyketide with a side-chain branching site that never appeared before from the nature.

Enzyme Inhibitors↗

PubMed2005

Improvement of single nucleotide polymorphism genotyping by allele-specific PCR using primers modified with an ENA residue.

When we placed an ENA residue into primers at the 3' end, or the n-1, n-2, or n-3 position, which included a single nucleotide polymorphism (SNP) site at the 3' end, only primers containing the ENA residue at the n-2 position were read by Taq DNA polymerase for amplification. The use of the ENA primers avoided the generation of undesired short products, which are thought to be derived from primer-dimers. A greater discrimination of the SNP site by these primers containing the ENA residue was observed compared with that of the corresponding unmodified DNA primers that are often used for allele-specific polymerase chain reaction (AS-PCR). This improvement is probably due to the difficulty of incorporating a nucleotide into the mismatched ENA primer by Taq DNA polymerase in the modified primer-template duplex. These results demonstrate that ENA primer-based AS-PCR would enable a rapid and reliable technique for SNP genotyping.

Alleles↗

PubMed2005

Comparison of enzymatic properties between hPADI2 and hPADI4.

In the sera of rheumatoid arthritis (RA) patients, autoantibodies directed to citrullinated proteins are found with high specificity for RA. Peptidylarginine deiminases (PADIs) are enzymes responsible for protein citrullination. Among many isoforms of PADIs, only PADI4 has been identified as an RA-susceptibility gene. To understand the mechanisms of the initiation and progression of RA, we compared the properties of two PADIs, human PADI2 and human PADI4, which are present in the synovial tissues of RA patients. We confirmed their precise distribution in the RA synovium and compared the stability, Ca2+ dependency, optimal pH range, and substrate specificity. Small but significant differences were found in the above-mentioned properties between hPADI2 and hPADI4. Using LC/MS/MS analysis, we identified the sequences in human fibrinogen indicating that hPADI2 and hPADI4 citrullinate in different manners. Our results indicate that hPADI2 and hPADI4 have different roles under physiological and pathological conditions. Further studies are needed for the better understanding of the role of hPADIs in the initiation and progression of RA.

Amino Acid Sequence↗

PubMed2003

Binding mode of ecdysone agonists to the receptor: comparative modeling and docking studies.

Three-dimensional structure models of the ligand-binding domain of the ecdysone receptor of Heliothis virescens were built by the homology modeling technique from the crystal structures of nuclear receptors. Two models were created based both on known ligand-binding domain structures of the receptors with the highest sequence identity to the ecdysone receptor, and on those of steroid hormone receptors. The latter model, which was found to have better stereochemical quality and be in good agreement with the binding of the steroidal framework of the endogenous agonist 20-hydroxyecdysone, was used for docking studies. The docking of 20-hydroxyecdysone to the receptor model revealed that the ligand molecule can interact with the receptor in a similar manner to other steroid hormone-receptor complexes. The docking of a dibenzoylhydrazine agonist, chromafenozide, was performed based on the correspondences between the molecule and 20-dydroxyecdysone expected by molecular comparison. The interactions of the ligands with the receptor in the complexes modeled were investigated and found to be consistent with known structure-activity relationships.

Amino Acid Sequence↗

PubMed2002

An efficient method for reconstructing protein backbones from alpha-carbon coordinates.

We present an approach for building protein backbones from alpha-carbon (Calpha) coordinates. The approach is analytical and based on the information of favored regions in the Ramachandran map. The backbone construction consists of three parts: prediction of (phi, psi) angle pairs from the Calpha trace, generation of atomic coordinates with these (phi, psi) angles, and refinement by subsequent energy minimization. Tests on several known protein structures show that the root mean square deviations in reconstructed backbones are 0.25-0.48 A for coordinates and 14-34 degrees for phi and psi angles. The results indicate that our method is one of the best methods proposed in terms of accuracy. It has also been revealed that the approach is not only robust against errors in Calpha coordinates but is also capable of providing equivalent or more reasonable models compared to other known methods. Furthermore, backbone structures were found to be built accurately by using the (phi, psi) angles from a different structure of the same protein. This suggests that the approach could be effective and useful in homology modeling studies.

Algorithms↗