Shirouzu M

References (3)

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

Title : Structure of the minimized alpha\/beta-hydrolase fold protein from Thermus thermophilus HB8 - Xie_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_993
Author(s) : Xie Y , Takemoto C , Kishishita S , Uchikubo-Kamo T , Murayama K , Chen L , Liu ZJ , Wang BC , Manzoku M , Ebihara A , Kuramitsu S , Shirouzu M , Yokoyama S
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 63 :993 , 2007
Abstract : The gene encoding TTHA1544 is a singleton found in the Thermus thermophilus HB8 genome and encodes a 131-amino-acid protein. The crystal structure of TTHA1544 has been determined at 2.0 A resolution by the single-wavelength anomalous dispersion method in order to elucidate its function. There are two molecules in the asymmetric unit. Each molecule consists of four alpha-helices and six beta-strands, with the beta-strands composing a central beta-sheet. A structural homology search revealed that the overall structure of TTHA1544 resembles the alpha/beta-hydrolase fold, although TTHA1544 lacks the catalytic residues of a hydrolase. These results suggest that TTHA1544 represents the minimized alpha/beta-hydrolase fold and that an additional component would be required for its activity.
ESTHER : Xie_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_993
PubMedSearch : Xie_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_993
PubMedID: 18084077
Gene_locus related to this paper: teth8-Q5SI36

Title : Crystal structure of TT1662 from Thermus thermophilus HB8: a member of the alpha\/beta hydrolase fold enzymes -
Author(s) : Murayama K , Shirouzu M , Terada T , Kuramitsu S , Yokoyama S
Ref : Proteins , 58 :982 , 2005
PubMedID: 15648092
Gene_locus related to this paper: theth-TT1662