Ihara K

References (2)

Title : Identification of plb1 mutation that extends longevity via activating Sty1 MAPK in Schizosaccharomyces pombe - Maekawa_2024_Mol.Genet.Genomics_299_20
Author(s) : Maekawa Y , Matsui K , Okamoto K , Shimasaki T , Ohtsuka H , Tani M , Ihara K , Aiba H
Ref : Mol Genet Genomics , 299 :20 , 2024
Abstract : To understand the lifespan of higher organisms, including humans, it is important to understand lifespan at the cellular level as a prerequisite. So, fission yeast is a good model organism for the study of lifespan. To identify the novel factors involved in longevity, we are conducting a large-scale screening of long-lived mutant strains that extend chronological lifespan (cell survival in the stationary phase) using fission yeast. One of the newly acquired long-lived mutant strains (No.98 mutant) was selected for analysis and found that the long-lived phenotype was due to a missense mutation (92Phe Ile) in the plb1(+) gene. plb1(+) gene in fission yeast is a nonessential gene encoding a homolog of phospholipase B, but its functions under normal growth conditions, as well as phospholipase B activity, remain unresolved. Our analysis of the No.98 mutant revealed that the plb1 mutation reduces the integrity of the cellular membrane and cell wall and activates Sty1 via phosphorylation.
ESTHER : Maekawa_2024_Mol.Genet.Genomics_299_20
PubMedSearch : Maekawa_2024_Mol.Genet.Genomics_299_20
PubMedID: 38424265

Title : Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery - Dileep_2022_Int.J.Biol.Macromol_210_172
Author(s) : Dileep KV , Ihara K , Mishima-Tsumagari C , Kukimoto-Niino M , Yonemochi M , Hanada K , Shirouzu M , Zhang KYJ
Ref : Int J Biol Macromol , 210 :172 , 2022
Abstract : Alzheimer's disease (AD) is one of the most common, progressive neurodegenerative disorders affecting the aged populations. Though various disease pathologies have been suggested for AD, the impairment of the cholinergic system is one of the critical factors for the disease progression. Restoration of the cholinergic transmission through acetylcholinesterase (AChE) inhibitors is a promising disease modifying therapy. Being the first marketed drug for AD, tacrine reversibly inhibits AChE and thereby slows the breakdown of the chemical messenger acetylcholine (ACh) in the brain. However, the atomic level of interactions of tacrine towards human AChE (hAChE) is unknown for years. Hence, in the current study, we report the X-ray structure of hAChE-tacrine complex at 2.85 A resolution. The conformational heterogeneity of tacrine within the electron density was addressed with the help of molecular mechanics assisted methods and the low-energy ligand configuration is reported, which provides a mechanistic explanation for the high binding affinity of tacrine towards AChE. Additionally, structural comparison of reported hAChE structures sheds light on the conformational selection and induced fit effects of various active site residues upon binding to different ligands and provides insight for future drug design campaigns against AD where AChE is a drug target.
ESTHER : Dileep_2022_Int.J.Biol.Macromol_210_172
PubMedSearch : Dileep_2022_Int.J.Biol.Macromol_210_172
PubMedID: 35526766
Gene_locus related to this paper: human-ACHE